Podcasts about somatostatin

Today's guest Ginger Vieira, tells us everything we need to know about the 5 hormones affected by T1D, which impact weight loss, appetite, and insulin sensitivity. We discuss each of these hormones in detail and the positive lifestyle choices we can make to work WITH our bodies instead of against them. We also candidly discuss using Ozempic for weight management in type ones. This is the stuff no one is taught at diagnosis! Time Stamps:  (04:54) The “Sorority Terms” of cells(6:40) Amalin hormone(7:42) Glucagon hormone & the overproduction of glucose(09:30) Weight management, hunger cues, & hormones(12:00) The role of protein in your diet (12:25) Glucagon continued (12:45) Somatostatin hormone (14:28) The liver and low blood sugar(16:40) Pancreatic polypeptide hormone & insulin sensitivity (22:08) Stress & basal insulin (22:30) The misunderstanding of the “dawn phenomenon”(23:49) Ghrelin hormone (26:45) Why crash diets do not work with T1D(27:42) Why lifestyle is crucial with T1D and caffeine's effect (28:44) The impact of exercise + insulin sensitivity (31:13) Ozempic (35:38) The importance of working with a coach while taking GLP 1 medicationWhat to do now: Follow me @lauren_bongiorno and @riselyhealth on Instagram to stay in the loop for when new episodes drop.Learn more about our 1:1 coaching programs HERE. Find Ginger @gingervieira.t1d and get her books HERE Disclaimer: Nothing you hear on the Reclaim your Rise podcast should be a substitute for personalized professional medical advice. Please always consult your physician or other medical professional before making any changes to your diet, insulin dosages, or healthcare plan. 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538511v1?rss=1 Authors: Chamberland, S., Grant, G., Machold, R. P., Nebet, E. R., Tian, G., Hanani, M., Kullander, K., Tsien, R. W. Abstract: Hippocampal somatostatin-expressing (Sst) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single cell transcriptome analyses have provided a comprehensive Sst-IN subtype census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of Sst-INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal Sst-INs that largely tiled the morpho-functional parameter space of the Sst-INs superfamily. Notably, the Sst;;Tac1 intersection revealed a population of bistratified INs that preferentially synapsed onto fast-spiking interneurons (FS-INs) and were both necessary and sufficient to interrupt their firing. In contrast, the Ndnf;;Nkx2-1 intersection identified a population of oriens lacunosum-moleculare (OLM) INs that predominantly targeted CA1 pyramidal neurons, avoiding FS-INs. Overall, our results provide a framework to translate neuronal transcriptomic identity into discrete functional subtypes that capture the diverse specializations of hippocampal Sst-INs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.22.533857v1?rss=1 Authors: Gamlin, C. R., Schneider-Mizell, C. M., Mallory, M., Elabbady, L., Gouwens, N., Williams, G., Mukora, A., Dalley, R., Bodor, A. L., Brittain, D., Buchanan, J., Bumbarger, D. J., Kapner, D., Kinn, S., Mahalingam, G., Seshamani, S., Takeno, M., Torres, R., Yin, W., Nicovich, P. R., Bae, J. A., Castro, M. A., Dorkenwald, S., Halageri, A., Jia, Z., Jordan, C., Kemnitz, N., Lee, K., Li, K., Lu, R., Macrina, T., Mitchell, E., Mondal, S. S., Mu, S., Nehoran, B., Popovych, S., Silversmith, W., Turner, N. L., Wong, W., Wu, J., Yu, S.-c., Berg, J., Jarsky, T., Lee, B., Seung, H. S., Zeng, H., Reid, R. C Abstract: Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types1. Neural cell types have previously been defined by morphology 2,3, electrophysiology 4,5, transcriptomic expression 6-8 , connectivity 9-13, or even a combination of such modalities 14-16. More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells 17-20. Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex 21. It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type 22,23 known to be Somatostatin positive (Sst+) 24,25, were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529922v1?rss=1 Authors: Michon, F.-X., Laplante, I., Bosson, A., Robitaille, R., Lacaille, J.-C. Abstract: Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward localization during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, "reward off sustained", "reward off transient", "reward on sustained" and "reward on transient", and these responses showed global remapping after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent spatial coding related to learning reward localization. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.16.528882v1?rss=1 Authors: Negwer, M., Bosch, B., Bormann, M., Hesen, R., Lütje, L., Aarts, L., Rossing, C., Nadif Kasri, N., Schubert, D. Abstract: Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory's use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2's CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline. For more precise alignment, we add a landmark-based atlas registration to ClearMap's functions as well as include young mouse reference atlases for developmental studies. We provide alternative cell segmentation method besides ClearMap's threshold-based approach: Ilastik's Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3D visualization of the annotated cells. As a proof-of-principle, we use FriendlyClearMap to quantify the distribution of the three main GABAergic interneuron subclasses (Parvalbumin+, Somatostatin+, and VIP+) in the mouse fore- and midbrain. For PV+ neurons, we provide an additional dataset with adolescent vs. adult PV+ neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.02.526850v1?rss=1 Authors: Hostetler, R. E., Hu, H., Agmon, A. Abstract: Of the four main subclasses of inhibitory cortical interneurons, somatostatin-containing (SOM) interneurons are the most diverse. Earlier studies identified layer 1-projecting (Martinotti) cells in layer 5/6 of the X98 and the Chrna2-cre transgenic lines, and two groups of non-Martinotti cells - long-range projecting SOM cells in layers 2 and 6, and layer 4-projecting X94 cells in layers 4 and 5. Later in-vivo and ex-vivo studies described two morphological types of Martinotti cells which appear to have opposing roles in behaving animals. More recently, large-scale transcriptomic studies attempting to classify all cortical neurons by their gene expression profiles and by their morphological and electrophysiological phenotypes divided all SOM interneurons into 13 morpho-electro-transcriptomic (MET) types. It remains unclear, however, how the previously identified SOM subtypes relate to each other, and how they map onto the suggested MET classification scheme. Importantly, only a small number of Cre or Flp driver line are available to target SOM interneurons, and there are currently no genetic tools to target the majority of the proposed MET types for recording, imaging or optogenetic manipulations, severely hindering progress on understanding the roles SOM interneurons play in sensorimotor processing or in learning and memory. To begin to overcome these barriers, we undertook a systematic examination of SOM interneuron subtypes in layer 5 of mouse somatosensory cortex. We generated 4 intersectional triple-transgenic genotypes, by crossing the Sst-IRES-Flp line with 4 different Cre lines and with a dual-color reporter that labels all Cre expressing SOM cells with GFP and all other SOM cells in the same brain with tdTomato. Brains from adult mice of both sexes were retrogradely labeled by epipial dye deposits, processed histologically, and immunostained for 3 marker proteins known to be expressed in different SOM subsets. By correlating fluorescent protein expression, retrograde label and marker proteins in the same neurons, we found that Cre-expressing SOM cells in the Calb2-IRES-Cre and in the Chrna2-Cre lines, and GFP expressing neurons in the X94 line, comprise three non-overlapping SOM populations which together account for about half of all SOM cell in layer 5. Using whole-cell recordings ex-vivo, we show that they also exhibit electrophysiological properties which are distinctly different from each other. This multimodal convergence of axonal projection target, marker protein expression and electrophysiological properties strongly suggests that these three populations can be considered bona-fide SOM subtypes. Indeed, each of the three subtypes appears to map onto a unique MET type. Our findings call for a renewed effort to generate additional driver lines that can be used combinatorially to provide genetic access to the many remaining SOM subtypes and uncover their roles in cortical computations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.06.522982v1?rss=1 Authors: Nagaeva, E., Schafer, A., Linden, A.-M., Elsila, L. V., Ryazantseva, M., Umemori, J., Egorova, K., Korpi, E. R. Abstract: Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Recently, we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighbouring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that VTA Sst neurons also project far outside the VTA and innervate several forebrain regions that are mainly involved in the regulation of emotional behaviour. When we deleted these VTA Sst neurons several behaviours and drug effects were affected, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to inescapable stress of forced swimming, often in a sex-dependent manner. Interestingly, the majority of these Sst projecting neurons was found to express Vglut2 and Th, but not Dat. Together, these data demonstrate that VTA Sst neurons have their selective projection targets, which are distinct from the main targets of VTA dopamine neurons and involved in the regulation of a variety of behaviours mostly associated with the stress response. This, in turn, makes these VTA neurons a meaningful addition to the somatostatinergic system of the brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.01.514756v1?rss=1 Authors: Nagarajan, R., Lyu, J., Kambali, M., Wang, M., Courtney, C. D., Christian-Hinman, C. A., Rudolph, U. Abstract: Aging is often associated with a decline in cognitive function. A reduction in the number of somatostatin-positive (SOM+) interneurons in the DG has been described in cognitively impaired but not in unimpaired aged rodents. However, it remains unclear whether the reduction in SOM+ interneurons in the DG hilus is causal for age-related cognitive dysfunction. We hypothesized that hilar (SOM+) interneurons play an essential role in maintaining cognitive function and that a reduction in the number of hilar (SOM+) interneurons might be sufficient to induce cognitive dysfunction. Hilar (SOM+) interneurons were ablated by expressing a diptheria toxin transgene specifically in these interneurons. An AAV-EF1-mCherry-flex-dtA construct was stereotaxically injected (bilaterally) into the DG hilus of young adult Sst-IRES-Cre mice, which resulted in an approximately 50% reduction in the number of SOM+ neurons and also a reduction in the number of GAD-67+ neurons in the DG hilus. c-Fos staining was increased in DG and CA3 but not in CA1. Behavioral testing, which started 21 days after the stereotaxic injections, revealed a reduced recognition index in the novel object recognition test, a reduction in the percentage of correct alternations in the Y maze tests, and increased latencies and path lengths in the learning and the reversal learning phase of the Morris water maze. Our results show that partial genetic ablation of SOM+ hilar interneurons is sufficient to increase activity in DG and CA3, as has been described to occur with aging, and to induce an impairment of learning and memory functions. Thus, partial ablation of hilar SOM+ interneurons may be a significant contributing factor to age-related cognitive dysfunction. These mice may also be useful as a cellularly defined model of hippocampal aging. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.05.511002v1?rss=1 Authors: Lyu, J., Nagarajan, R., Kambali, M., Wang, M., Rudolph, U. Abstract: The cellular basis of age-related impairments of hippocampal function is not fully understood. In order to evaluate the role of somatostatin-positive (Sst+) interneurons in the dentate gyrus hilus in this process, we chemogenetically inhibited Sst+ interneurons in the dentate gyrus (DG) hilus. Chronic chemogenetic inhibition (CCI) of these neurons resulted in increased c-Fos staining in the DG hilus, a decrease in the percentage of Gad67- and of Sst-expressing neurons in the DG, and increased microglial activation in DG, CA3, and CA1. Total dendritic length and spine density were reduced in DG and CA1, suggesting reduced dendritic complexity. Behaviorally, the recognition index in an object recognition task and the percentage of spontaneous alternations in the Y maze were decreased, while in both initial and reversal learning in the Morris water maze the latencies to find the hidden platform were increased, suggesting cognitive dysfunction. Our findings establish a causal role for a reduced function of Sst+ interneurons in the DG hilus for cognitive decline and suggest that this reduced function may contribute to age-related impairments of learning and memory. Our CCI mice may represent a cellularly defined model of hippocampal aging. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.30.510330v1?rss=1 Authors: Espinosa, N., Caneo, M., Alonso, A., Moran, C., Fuentealba, P. Abstract: The septal complex regulates both motivated and innate behaviors, chiefly by the action of its diverse population of long-range projection neurons. Among those cells are lateral septum somatostatin neurons which collateral axons profusely innervate cortically-projecting neurons located in the medial septum. Thus, somatostatin cells are ideally positioned at the crossroads of ascending and descending modulatory pathways, likely supporting functional roles in both anatomical directions. Here, we used optogenetic stimulation and extracellular recordings in acutely anesthetized transgenic mice to show that septal somatostatin neurons can disinhibit the cholinergic septo-hippocampal pathway, thus enhancing the amplitude and synchrony of theta oscillations, while depressing sharp wave ripple episodes in the dorsal hippocampus. Nonetheless, photosuppressing septal somatostatin cells hindered goal-directed behavior in a spatial memory task by disrupting task engagement, evidenced in increased immobility, followed by repetitive self-grooming, a hallmark innate behavior. These results suggest that septal somatostatin cells can recruit ascending cholinergic pathways to promote hippocampal theta oscillations, while gating repetitive displacement behaviors mediated by descending subcortical pathways. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.29.510081v1?rss=1 Authors: Wu, J. S., Sevier, E., Saldi, G.-A., Yu, S., Abbott, L., Choi, D. H., Sherer, M., Qiu, Y., Shinde, A., Rizzo, D., Xu, Q., Barrera, I., Kumar, V., Marrero, G., Pörnneke, A., Huang, S., Rudy, B., Stafford, D. A., Macosko, E., Chen, F., Fishell, G. Abstract: The cardinal interneuron classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings glosses over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. The organizing principles by which the connectivity of these subtypes is specified are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes. Using these strategies to target three subtypes that span the entire cortical column, we examined their afferent and efferent connectivity. Our data demonstrated that each of these possesses remarkable reciprocal connectivity with the intracortical or corticofugal pyramidal classes, as well as parvalbumin interneurons. Even when two interneuron subtypes shared the same efferent target, their synaptic targeting proved selective for particular dendritic compartments. We thus provide evidence that subtypes of somatostatin cortical interneurons form cell-type specific cortical circuits. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.26.509540v1?rss=1 Authors: Williams, D., Yan, B. Q., Wang, H., Negm, L., Sackmann, C., Verkuyl, C., Rezai-Stevens, V., Eid, S., Sato, C., Watts, J. C., Wille, H., Schmitt-Ulms, G. Abstract: The molecular underpinnings that govern the endoproteolytic release of the amyloid beta peptide (Abeta) from the amyloid precursor protein (APP) are now quite well understood. The same cannot be said for the events that precipitate the aggregation and amyloid deposition of Abeta in Alzheimer's disease (AD). The 14-amino-acid cyclic neuroendocrine peptide somatostatin (SST-14) has long been thought of as playing a role, foremost by controlling the expression of the Abeta clearing enzyme neprilysin, and more recently by directly interacting with Abeta oligomers. Missing have been in vivo data in a relevant Abeta amyloidosis model. Here we addressed this shortcoming by crossing AppNL-F/NL-F mice with Sst-deficient mice of identical genetic background to assess if and how the presence of Sst influences key pathological hallmarks of Abeta amyloidosis that develop in AppNL-F/NL-F mice after 10 months of age. Surprisingly, we found that Sst had no influence on whole brain neprilysin transcript, protein or activity levels, an observation that cannot be accounted for by a compensatory upregulation of the Sst paralog, cortistatin (Cort), that we observed in 15-month-old Sst-deficient mice. The absence of Sst did lead to a subtle but significant increase in the density of cortical Abeta amyloid plaques. Follow-on western blot analyses of whole brain extracts indicated that Sst interferes with early steps of Abeta assembly that manifest in Sst null brains through the appearance of SDS-stable smears of 55-150 kDa. As expected, no effect of Sst on tau steady-state levels or its phosphorylation were observed. Results from this study are easier reconciled with an emerging body of data that point toward Sst affecting Abeta amyloid plaque formation through direct interference with Abeta aggregation rather than through its effects on neprilysin expression. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Insulin Intro Hormone that signals cells throughout the human body to intake energy, and promote various performance and recovery based outcomes.  Body Modifying the activity of enzymes and the resulting reactions in the body. glycogen and fat synthesis from glucose are stimulated, and glucose production by the liver through glycogenolysis and gluconeogenesis are inhibited.[68] The breakdown of triglycerides by adipose tissue into free fatty acids and glycerol is also inhibited.[68] Building muscle following sickness or injury via the transportation of amino acids to the muscle tissue, which is required to repair muscular damage and increase size and strength. It helps to regulate the uptake of amino acids, DNA replication, and the synthesis of proteins. Managing the synthesis of lipids by uptake into fat cells, which are converted to triglycerides. Uptake of amino acids and potassium into the cells that cannot take place in the absence of insulin. Managing the excretion of sodium and fluid volume in the urine. Enhancing the memory and learning capabilities of the brain. Alzeimers patients had increased memory recall with hyperinsulemia and with hyperglycemia (due to consumption of sugars). Hyperglycemia with insulin suppression via Somatostatin had no positive effect on memory recall. Dave questions Glycemic index carbs - should the score on these matter and should you take low vs high index food pre vs post workout Carb timing - is it really important to time carbs (perhaps pre, intra, and post workout) before you sleep to avoid increasing fat synthesis? Why is it that some people can do a low or no carb diet and make gains while others need a moderate level of carbs fats and proteins? Controlling overall caloric intake, does the complexity of the carb matter? Why is the a war on carbs? Is it a good marketing ploy or something more legit? Fasted training - have you seen there to be any merit to it in regards to increased fat loss? How much does controlling sugar intake assist with body recomposition compared to carb intake? What about those that are pre-diabetic or morbidly obese? Does that mean a person isn't as insulin sensitive?  Conclusions Insulin is highly anabolic and starts a cascade of events that result in more energy storage in muscle cells, recovery, hypertrophy, and hyperplasia. Insulin is also converted by the liver to IGF-1 and higher levels of insulin result in more IGF-1. Carbs are just as key to performance and recovery as proteins.     

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.12.507622v1?rss=1 Authors: Kiritani, T., Pala, A., Gasselin, C., Crochet, S., Petersen, C. C. Abstract: Neocortical neurons can increasingly be divided into well-defined classes, but their activity patterns during quantified behavior remain to be fully determined. Here, we obtained membrane potential recordings from various classes of excitatory and inhibitory neurons located across different cortical depths in the primary whisker somatosensory barrel cortex of awake head-restrained mice during quiet wakefulness, free whisking and active touch. Excitatory neurons, especially those located superficially, were hyperpolarized with low action potential firing rates relative to inhibitory neurons. Parvalbumin-expressing inhibitory neurons on average fired at the highest rates, responding strongly and rapidly to whisker touch. Vasoactive intestinal peptide-expressing inhibitory neurons were excited during whisking, but responded to active touch only after a delay. Somatostatin-expressing inhibitory neurons had the smallest membrane potential fluctuations and exhibited hyperpolarising responses at whisking onset for superficial, but not deep, neurons. Interestingly, rapid repetitive whisker touch evoked excitatory responses in somatostatin-expressing inhibitory neurons, but not when the intercontact interval was long. Our analyses suggest that distinct genetically-defined classes of neurons at different subpial depths have differential activity patterns depending upon behavioral state providing an important basis for constraining future computational models of neocortical function. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

In today's podcast Dr. Lewis Blevins reviews and summarizes information on the usage of Somatostatin Analogues in the treatment and management of acromegaly.

This episode covers somatostatin!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.27.358267v1?rss=1 Authors: Ng, S. Y., Lee, A. T.-H., Ariffin, M. Z., Woon, P. J., Chng, T. S. H., Khanna, S. Abstract: The forebrain medial septum (MS), implicated in affective-motivational behaviours, is enriched in substance P (SP) sensitive neurokinin-1 receptors (NK1R) and somatostatin (SST) receptors (SSTR) that are located almost exclusively on cholinergic and GABAergic neurons, respectively. However, the physiological function of these receptors is poorly understood. This study characterized the actions of intraseptal SP on electrophysiological indices of septo-hippocampal activation, then utilised NK1 receptor antagonist, L-733,060, and SST to investigate the physiological role of endogenous neurotransmission at NK1R, and SST-sensitive mechanisms, in novel open field and formalin test of inflammatory pain. The findings showed that neurotransmission at NK1R mediates formalin-induced electrophysiological responses in the septo-hippocampus in anaesthetized and behaving animals. Furthermore, parallel NK1R- and SST-sensitive mechanisms affect different aspects of animal behaviours in both tests, collectively modulating attention and habituation in open field and driving formalin-induced nociception. This brings out a newer peptidergic dimension of septal physiology in nociception. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.28.313056v1?rss=1 Authors: Ponserre, M., Fermani, F., Klein, R. Abstract: In order to successfully forage in an environment filled with rewards and threats, animals need to rely on familiar structures of their environment that signal food availability. The central amygdala (CeA) is known to mediate a panoply of consummatory and defensive behaviors, yet how specific activity patterns within CeA subpopulations guide optimal choices is incompletely understood. In a paradigm of appetitive conditioning in which mice freely forage for food across a continuum of cues, we find that two major subpopulations of CeA neurons, Somatostatin-positive (CeASst) and protein kinase C{delta}-positive (CeAPKC{delta}) neurons can assign motivational properties to environmental cues and encode memory of goal location. While the proportion of food responsive cells was higher within CeASst than CeAPKC{delta} neurons, only the activities of CeAPKC{delta}, but not CeASst, neurons were required for learning of contextual food cues. Since CeAPKC{delta} neurons are known to promote a range of defensive behaviors, our findings point to a model in which CeA circuit components are not organized in specialized functional units but can process both aversive and rewarding information in a context and experience dependent manner. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.26.314104v1?rss=1 Authors: Weir, K., Kim, D. W., Blackshaw, S. Abstract: Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a dose-dependent inhibition of photoreceptor generation while increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants and abolished in Sstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed in Sstr2-deficient retinas in vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, although in vivo Sstr2 is dispensable for normal retinal development. Copy rights belong to original authors. Visit the link for more info

Today we will be talking about 2 case studies concerning Somatostatin, a procedure known as the Whipple Operation, and common plans of action to deal with Somatostatinoma.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.02.233080v1?rss=1 Authors: Delorme, J., Kuhn, F. R., Wang, L., Kodoth, V., Ma, J., Jiang, S., Aton, S. Abstract: Sleep loss profoundly disrupts consolidation of hippocampus-dependent memory. To better characterize effects of learning and sleep loss on the hippocampal circuit, we quantified activity-dependent phosphorylation of ribosomal subunit S6 (pS6) across the dorsal hippocampus of mice. We find that pS6 in enhanced in the dentate gyrus (DG) following single-trial contextual fear conditioning (CFC), but is reduced throughout the hippocampus after brief sleep deprivation (SD), a manipulation which disrupts contextual fear memory (CFM) consolidation. To characterize cell populations with activity affected by SD, we used translating ribosome affinity purification (TRAP)-seq to identify cell type-specific transcripts on pS6 ribosomes after SD vs. sleep. Cell type-specific enrichment analysis (CSEA) of these transcripts revealed that hippocampal somatostatin-expressing (Sst+) interneurons, and cholinergic and orexinergic inputs to hippocampus, are selectively activated after SD. We used TRAP targeted to hippocampal Sst+ interneurons to identify cellular mechanisms mediating SD-driven Sst+ interneuron activation. We next used pharmacogenetics to mimic the effects of SD, selectively activating hippocampal Sst+ interneurons while mice slept in the hours following CFC. We find that activation of Sst+ interneurons is sufficient to disrupt CFM consolidation, by gating activity in surrounding pyramidal neurons. Pharmacogenetic inhibition of cholinergic input to hippocampus from the medial septum (MS) promoted CFM consolidation and disinhibited neurons in the DG, increasing pS6 expression. This suggests that state-dependent gating of DG activity is mediated by cholinergic input during SD. Together these data provide evidence for an inhibitory gate on hippocampal information processing, which is activated by sleep loss. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.179671v1?rss=1 Authors: Tossell, K., Yu, X., Anuncibay Soto, B., Vicente, M., Miracca, G., Giannos, P., Miao, A., Hsieh, B., Ma, Y., Yustos, R., Vyssotski, A. L., Constandinou, T., Franks, N. P., Wisden, W. Abstract: Animals undertake specific behaviors before sleep. Little is known about whether these innate behaviors, such as nest building, are actually an intrinsic part of the sleep-inducing circuitry. We found, using activity-tagging genetics, that mouse prefrontal cortex (PFC) somatostatin/GABAergic (SOM/GABA) neurons, which become activated during sleep deprivation, induce nest building when opto-activated. These tagged neurons induce sustained global NREM sleep if their activation is prolonged metabotropically. Sleep-deprivation-tagged PFC SOM/GABA neurons have long-range projections to the lateral preoptic (LPO) and lateral hypothalamus (LH). Local activation of tagged PFC SOM/GABA terminals in LPO and the LH induced nesting and NREM sleep respectively. Our findings provide a circuit link for how the PFC responds to sleep deprivation by coordinating sleep preparatory behavior and subsequent sleep. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.23.156018v1?rss=1 Authors: Stujenske, J. M., O'Neill, P.-K., Nahmoud, I., Goldberg, S., Diaz, L., Labkovich, M., Hardin, W., Bolkan, S. S., Reardon, T. R., Spellman, T. J., Salzman, C. D., Gordon, J. A., Likhtik, E. Abstract: The amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) activate specifically during learned non-threatening cues and block sensory-evoked phase resetting of theta-oscillations. SOM activation is PL-dependent, and prevents generalization. Thus, fear discrimination engages PL-dependent coordination of BLA responses to non-threatening stimuli. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.26.113373v1?rss=1 Authors: de Filippo, R., Rost, B., Stumpf, A., Cooper, C., Tukker, J., Harms, C., Beed, P., Schmitz, D. Abstract: Serotonin (5-HT) affects multiple physiological processes in the brain and is involved in a number of psychiatric disorders. 5-HT axons reach all cortical areas; however, the precise mechanism by which 5-HT modulates cortical network activity is not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SO), a synchronized cortical network activity universally present across species. SO are observed during slow-wave sleep and anesthesia and are considered the default cortical activity pattern. Combining opto- and pharmacogenetic manipulations with electrophysiological recordings, we discovered that 5-HT inhibits SO within the entorhinal cortex (EC) by activating somatostatin-expressing (Som) interneurons via the 5-HT2A receptor (5-HT2AR). This receptor is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, suggesting that 5-HT targeting of Som interneurons may play an important role in these processes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.22.103481v1?rss=1 Authors: Bruzsik, B., Biro, L., Zelena, D., Sipos, E., Szebik, H., Sarosdi, K. R., Horvath, O., Farkas, I., Csillag, V., Finszter, C. K., Mikics, E., Toth, M. Abstract: Excessive fear learning and extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in fear learning and expression is still not clarified. Here, we tested how BNST modulates fear learning in mice using a chemogenetic approach. Activation of GABAergic neurons of BNST during fear acquisition, more specifically the consolidation phase, resulted in enhanced cued fear recall. Importantly, BNST activation had no acute impact on fear expression during conditioning or recalls, but it enhanced cued fear recall subsequently, potentially via altered activity of downstream regions as indicated by c-Fos. Enhanced fear memory consolidation could be replicated by selectively activating somatostatin neurons (but not corticotropin releasing factor neurons), suggesting significant modulation of fear memory strength by specific circuits of BNST. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.087791v1?rss=1 Authors: Dobrzanski, G., Lukomska, A., Zakrzewska, R., Posluszny, A., Kanigowski, D., Urban-Ciecko, J., Liguz-Lecznar, M., Kossut, M. Abstract: Learning-related plasticity in the cerebral cortex is linked to the action of disinhibitory circuits of interneurons. Pavlovian conditioning, in which stimulation of the vibrissae is used as conditioned stimulus, induces plastic enlargement of the cortical functional representation of vibrissae activated during conditioning, visualized with [14C]-2-deoxyglucose (2DG). Using layer-specific, cell-selective DREADD transductions, we examined the involvement of somatostatin- (SOM-INs) and vasoactive intestinal peptide (VIP-INs)-containing interneurons in the development of learning-related plastic changes. We injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to activated vibrissae. The activity of interneurons was modulated during training, and 2DG maps were obtained 24 h later. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation and the conditioned reaction were absent. No effect of inhibiting VIP-INs was found. We report that the activity of L4 SOM-INs is indispensable for learning-induced plastic change. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.09.085795v1?rss=1 Authors: Nilsson, P., Sorgjerd, K., Kakiya, N., Sasaguri, H., Shimozawa, M., Tsubuki, S., Takamura, R., Zhou, Z., Loera-Valencia, R., Sekiguchi, M., Petrish, A., Schulz, S., Saito, T., Winblad, B., Saido, T. Abstract: Alzheimer's disease (AD) brains are characterized by increased levels of the pathogenic amyloid beta (Abeta) peptide, which accumulates into extracellular plaques. Finding a way to lower Abeta levels is fundamental for the prevention and treatment of AD. Neprilysin is the major Abeta-degrading enzyme which is regulated by the neuropeptide somatostatin. Here we used a combination of in vitro and in vivo approaches to identify the subtype specificity of the five somatostatin receptors (SSTs) expressed in the brain, involved in the regulation of neprilysin. Using a battery of Sst double knockout (dKO) mice we show that neprilysin is regulated by SST1 and SST4 in a redundant manner. Sst1 and Sst4 dKO mice exhibit a specific decrease of presynaptic neprilysin in the Lacunosum molecular layer. Moreover, a genetic deficiency of Sst1 and Sst4 in amyloid beta precursor protein (App) knock-in mice, an AD mouse model, aggravates the Abeta pathology in the hippocampus. As a first proof of concept towards an Abeta-lowering strategy involving neprilysin, we demonstrate that treatment with an agonist selective for SST1 and SST4 ameliorates the Abeta pathology and improves cognition in the App knock-in AD mouse model. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.06.081877v1?rss=1 Authors: Hoseini, M. S., Higashikubo, B., Cho, F. S., Chang, A. H., Clemente-Perez, A., Lew, I., Stryker, M. P., Paz, J. T. Abstract: Visual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma oscillations in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating visual perception remains unknown. Here we show that somatostatin-expressing neurons (SOM) in the nRT preferentially project to visual thalamic nuclei, as compared to the more abundant parvalbumin-expressing neurons, and powerfully modulate both visual information transmission and gamma oscillations in the primary visual cortex (V1). These findings represent a novel circuit through which the nRT can influence representation of visual information. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.30.068924v1?rss=1 Authors: Smith, C. J., Kingsbury, M. A., Dziabis, J. E., Hanamsagar, R., Malacon, K. E., Tran, J. N., Norris, H. A., Gulino, M., Bilbo, S. D. Abstract: Decreases in social behavior are a hallmark aspect of acute sickness behavior in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNF alpha; and IL-1 beta) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling. Copy rights belong to original authors. Visit the link for more info

Dr. Robert Ramirez, a member of the American Society of Clinical Oncology (ASCO), and NET nurse navigator Pam Ryan discuss the importance of the multidisciplinary team, building trust, and creating positive treatment experiences for patients with gastrointestinal and pancreatic NETs (GEP-NETs). (c) 2020 Ipsen Biopharmaceuticals, Inc. January 2020 SMD-US-003644

Session 29 Which of these neurotransmitters is mostly likely causing this patient’s galactorrhea and secondary amenorrhea? Where is it coming from? Dr. Karen Shackelford from BoardVitals. When you're looking to prepare for your Step 1 or Level 1 board exams, check out how BoardVitals can help you. You can find all their amazing QBanks for Step1, Level 1, or even any of your SHELF exams. Use the coupon code BOARDROUNDS to save 15% off. Listen to this podcast episode with the player above, or keep reading for the highlights and takeaway points. [01:37] Question of the Week A 34-year-old woman presents with amenorrhea for six months (secondary amenorrhea). Her menstrual cycles have been regular until this episode. She has, most of her life, a period every 28 days with a menstrual period that lasted three days. Today, on exam, a white nipple discharge is noted. A test for urine hCG is negative. Which of the following neurotransmitters suppresses the release of the hormone responsible for her condition? (A) Dopamine (B) Insulin (C) Serotonin (D) Somatostatin (E) Vasopressin [Related episode: Why Is This Menstruating Patient So Sick?] [02:50] Thought Process Behind the Correct Answer The correct answer here is A. If you think about the treatment for prolactinoma, where prolactin is released from the anterior pituitary, bromocriptine and cabergoline are used to shrink the prolactinoma. They're both dopamine agonists. The patient's symptoms are suggestive of prolactinoma. It's not totally obvious though as there wasn't headaches or visual field issues mentioned. Nevertheless, prolactinoma is the most common of all pituitary adenomas. It's also the most common cause of galactorrhea. The clinical features include amenorrhea, galactorrhea, and infertility. The prolactin normally stimulates the mammary glands to produce milk and inhibits the secretion of gonadotropin-releasing hormone, which results in amenorrhea and infertility. With large tumors, like the compression of the optic chiasm that results in bitemporal hemianopsia. Dopamine is normally used to suppress and release the prolactin. When you're not breastfeeding after birth, this becomes an issue. [05:15] Understanding the Incorrect Answers Insulin is produced by the pancreas and it's necessary for the uptake and utilization of glucose. Serotonin agonist is available in several classes, used as antidepressants. They're used to treat migraines, but not for prolactinoma. Additionally, some antipsychotic agents interfere with prolactin. Somatostatin is a hormone secreted by the pancreas that inhibits secretion of insulin and glucagon. It reduces the activity to digest the system. It's not receptive to dopamine and not related to galactorrhea. Vasopressin is an antidiuretic hormone and it's not affected by dopamine agonist. [06:22] Key Takeaways The key concept is that prolactinoma is probably the most common type of pituitary tumor and is the most common cause of galactorrhea. The symptoms occur because prolactin stimulates the mammary glands and suppresses GnRH, causing amenorrhea and infertility. The dopamine agonist suppresses prolactin secretion and shrinks the prolactinoma. Links: BoardVitals (coupon code BOARDROUNDS to save 15% off)

Dr. Andrew Hendifar, medical oncology lead for the Gastrointestinal Disease Research Group at Cedars-Sinai Medical Center, discusses a hypothetical patient with nonfunctional pancreatic NET. Dr. Hendifar provides practice pointers on disease presentation, tumor characteristics, diagnosis, and a 1st-line treatment option. Patient perspectives on this episode are voiced by actors, and represent hypothetical cases. Dr. Hendifar is a paid consultant for Ipsen. © 2020 Ipsen Biopharmaceuticals, Inc. April 2020. SMD-US-003939

In this episode I cover acromegaly.If you want to follow along with written notes on acromegaly go to zerotofinals.com/acromegaly or find the endocrinology section in the Zero to Finals medicine book.This episode covers the pathophysiology, presentation, causes, investigations and management of acromegaly. We also discuss bitemporal hemianopia. 

Dr Stephen Betz of Crinetics Pharmaceuticals talks with NEN at ICN 2018 Toronto about his research on the development of treatments for acromegaly; a condition where a pituitary adenoma causes growth hormone hypersecretion causing gigantism in children and abnormal growths in adults. Interview by Dr. Julie Ann Lough

Welcome to The Nutritional Pearls Podcast! Focusing on topics that include digestion, adrenal fatigue, leaky gut, supplementation, electrolytes, stomach acid, and so much more, “The Nutritional Pearls Podcast” features Christine Moore, NTP and is hosted by Jimmy Moore, host of the longest running nutritional podcast on the Internet.  Sharing nuggets of wisdom from Christine's training as a Nutritional Therapy Practitioner and Jimmy's years of podcasting and authoring international bestselling health and nutrition books, they will feature a new topic of interest and fascination in the world of nutritional health each Monday. Listen in today as Christine and Jimmy talk all about the endocrine system in Episode 15. Here's what Christine and Jimmy talked about in Episode 15: 1. What is the Endocrine System? The collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood, among other things. 2. Definition of hormones: Regulatory substances produced in an organism and transported in tissue fluids such as blood to stimulate specific cells or tissues into action. 3. Glands of the endocrine system and the minerals they depend on: A. Hypothalamus: Located in the brain, this is the part of the brain that controls the endocrine system. Think of it as a control center. It links the nervous system to the endocrine system through the Pituitary Gland. It releases at least 7 to 8 hormones that control the Pituitary Gland. The hypothalamus needs chromium for good health. 1. Thyrotropin-releasing Hormone (TRH)-a releasing hormone produced by the hypothalamus that stimulates the release of thyrotropin (thyroid-stimulating hormone or TSH) and prolactin from the pituitary gland. 2. Gonadotropin-releasing Hormone (GnRH)-signals the pituitary gland to create two hormones called leutenizing hormone (LH) and follicle-stimulating hormone (FSH) 3. Growth Hormone-releasing Hormone (GHRH)-stimulates the pituitary gland to produce and release growth hormone into the bloodstream. Once growth hormone is releases into the blood, it has an affect on just about every tissue of the body to control metabolism and growth. 4. Corticotropin-releasing Hormone (CRH)-Its main function is to stimulate the pituitary gland to produce Adrenocorticotropic Hormone (ACTH) 5. Somatostatin - it regulates the secretion of hormones coming from the pituitary gland, including growth hormone and thyroid stimulating hormone. It also inhibits the secretion of pancreatic hormones which include Glucagon and Insulin 6. Dopamine - this functions as a neurotransmitter which is a chemical released by neurons or nerve cells to send signals to other nerve cells. The brain has many distinct dopamine pathways and one of these pathways plays a big role in reward-motivated behavior. B. The Pituitary Gland: Located in the brain, it has also been described as the “master gland” because it secretes hormones that control other endocrine glands. It needs manganese for good health 1. Oxytocin-controls key aspects of the reproductive system and some aspects of human behavior 2. Prolactin-hormone that helps women produce milk after childbirth and it's important to both male and female reproductive health 3. Leutenizing Hormone-triggers ovulation and stimulates the production of testosterone 4. Anti-diuretic Hormone (ADH)-tells your kidneys how much water to conserve; it also constantly regulates and balances the amount of water in your blood 5. Human Growth Hormone (HGH)-encourages growth in children and adolescents, helps to regulate body composition as well as bodily fluids and muscle and bone growth, helps regulate sugar and fat metabolism, and it possibly helps with heart function C. The Pineal Gland also known as the Third Eye: This gland is also in the brain and it produces melatonin which helps with circadian rhythm. It is also known as the Third Eye because the Third Eye chakra in the Hindu system is located in the center of the forehead which is near the pineal gland. It depends on iodine and boron for good health. D. The Thyroid Gland: It depends on iodine and tyrosine. It is located in the front of the neck just below the Adams apple and is considered to be one of the major glands in the regulation of metabolism. It produces: 1. thyroxine (T4) which gets converted to its active form, triiodothyronine (T3) with the help of selenium. T3 controls basil metabolic rate 2. Calcitonin-responsible for the uptake of calcium to the bone E. The Parathyroid Gland: It's located in the neck behind the thyroid and produces parathormone or PTH which is associated with the growth of muscle and bone and distribution of calcium and phosphate in the body. It depends on calcium for good health. F. The thymus: The thymus lays across the trachea and bronchi in the upper thorax. It produces thymosin which triggers the immune system by activating the T-Cells and T-Lymphocytes which are white blood cells associated with antibody production. The thymus needs zinc for good health. G. The pancreas: It lies behind the stomach and needs chromium for good health. The pancreas produces: 1. Insulin by the Beta Cells which is responsible for the conversion of glucose to glycogen, shuttling glucose into the cells, and the conversion of excess glucose to fat 2. Glucagon by the Alpha Cells which is responsible for the conversion of glycogen to glucose H. The adrenal glands: They are on top of the kidneys and they rely on copper for good health. They produce: 1. Adrenalin which prepares the body for fight or flight 2. noradrenalin-which has similar effects to adrenalin 3. corticosteroids that include cortisol, cortisone, and corticosterone I. The ovaries: They are located in the lower abdomen and they rely on selenium for good health. They produce: 1. Estrogen which is responsible for the break-down of the uterus wall 2. progesterone which builds up and maintains the uterus wall for embedding of fertilized egg and is also associated with body hair, breast enlargement, and physical changes in the body J. The testes: They're located outside the pelvic cavity and produce testosterone which is responsible for the development and function of male sex organs and is associated with body hair, muscle development, and voice change. They rely heavily on selenium for good health. K. The prostate: It's about the size of a walnut located between the bladder and the penis. It produces prostate-specific antigen (PSA) which help keep the sperm in liquid form. The prostate relies on zinc for good health. 4. People with different endocrine issues carry weight on specific parts of the body A. If someone has adrenal gland problems through prolonged stress, cortisol is released and stores fat around the most vital organs which are in your midsection. Thus, a person with adrenal issues will carry more weight around their midsection. B. People with thyroid issues tend to carry weight all over since the thyroid controls the metabolism in all of your cells. C. For people with problems with their ovaries, they will tend to carry extra weight around their hips and lower stomach area. D. If a person has liver problems, they will tend to carry extra weight around their body but have thin legs 5. Blood sugar imbalances mess up the entire endocrine system because not only are the pancreas, liver, and adrenal glands all necessary for blood sugar regulation but they are also heavily involved in the endocrine system. Nutritional Pearl for Episode 15: It is very important to make sure blood sugar levels are normalized and under control before addressing any endocrine problem you have because blood sugar imbalances disrupt the entire endocrine system. BECOME A NUTRITIONAL THERAPY PRACTITIONER Sign up for the 9-month program NOTICE OF DISCLOSURE: Paid sponsorship YOUR NEW KETO DIET ALLY NOTICE OF DISCLOSURE: Paid sponsorship LINKS MENTIONED IN EPISODE 15 – SUPPORT OUR SPONSOR: Complete nutriton for nutritional ketosis (COUPON CODE LLVLC FOR 10% OFF YOUR FIRST ORDER) – SUPPORT OUR SPONSOR: Become A Nutritional Therapy Practitioner – NutritionalTherapy.com

This podcast describes the evolving role of Gallium-68 somatostatin-receptor PET imaging in the evaluation of patients with well-differentiated neuroendocrine tumors, and compares the diagnostic sensitivity of this imaging modality to conventional scans.

The majority of neuroendocrine tumors (NETs) of thegastro-enteropancreatic system coexpress sornatostatin receptors (SSTRs)and dopamine type 2 receptors (D2R), thus providing a rationale for theuse of novel SSTR2/D2R chimeric compounds in NET disease. Here weinvestigate the antitumor potential of the SSTR2/D2R chimeric compoundsBIM-23A760 and BIM-23A758 in comparison to the selective SSTR2 agonistBIM-23023 and the selective D2R agonist BIM-53097 on human NET celllines of heterogeneous origin. While having only minor effects on humanpancreatic and bronchus carcinoid cells (BONI and NCI-H727), BIM-23A758induced significant antitumor effects in human midgut carcinoid cells(GOT1). These effects involved apoptosis induction as well as inhibitionof mitogen-activated protein kinase and Akt signaling. Consistent withtheir antitumor response to BIM-23A758, GOT1 cells showed relativelyhigh expression levels of SSTR2 and D2R mRNA. In particular, GOT1 cellshighly express the short transcript variant of D2R. In contrast toBIM-23A758, the SSTR2/D2R chimeric compound BIM-23A760 as well as theindividual SSTR2 and D2R agonistic compounds BIM-23023 and BIM-53097induced no or only minor antitumor responses in the examined NET celllines. Taken together, our findings suggest that the novel SSTR2/D2Rchimeric compound BIM-23A758 might be a promising substance for thetreatment of NETs highly expressing SSTR2 and D2R. In particular, asufficient expression of the short transcript variant of DR2 might playa pivotal role for effective treatment.

Prostate

Die vorliegende Arbeit hatte zum Ziel, die prinzipielle Fragestellung zu beantworten, ob Stammzellen aus humanen Haarfollikeln in ausreichender Menge expandiert werden können und inwieweit eine Differenzierung in neuroendokrine Zellen möglich ist. Es sollte eine Methode zur Isolierung und Langzeitkultivierung von Haarfollikelstammzellen etabliert und optimiert werden, um eine neue Quelle autologer adulter Stammzellen für zelltherapeutische Ansätze zu gewinnen. Durch Verwendung verschiedener Medien und Beschichtungsarten wurde ein Protokoll entwickelt, aus Dispase-verdauten Hautbiopsien Progenitorzellen zu isolieren. Die auf diese Weise expandierten Zellen wurden mit FACS-Analyse, RT-PCR und Immunhistologie charakterisiert. Im letzten Teil der Arbeit wurde durch Zugabe von spezifischen Faktoren die Fähigkeit zur Differenzierung in unterschiedliche Zelltypen untersucht. Nach Austestung verschiedener Zellkulturbedingungen wurde eine neue Population von Zellen aus der Haarfollikelregion isoliert. Diese Zellen, die als hBSCs bezeichnet wurden, waren über mehr als 30 Passagen mit stabilem Phänotyp kultivierbar (Self-Renewal). Zudem waren sie im Colony-Unit-Assay positiv und zeigten die Expression pluripotenter (Oct4) und multipotenter Stammzellmarker (Nestin, BCRP1, Sox2). Die molekulare Signatur der hBSCs zeigt einige Übereinstimmung mit Merkelzellen, neuroektodermalen Zellen der Haut, die eine Rolle als Mechanorezeptoren und neurosekretorische Zellen der Haut spielen. Unter Verwendung von etablierten Protokollen wurde die Fähigkeit der Differenzierung in Adipozyten, Osteoblasten, glatte Muskelzellen, Neuronen und endokrine Zellen untersucht. Der Nachweis der Entwicklung von glatten Muskelzellen, Neuronen und in eingeschränktem Maße auch Adipozyten belegt die Multipotenz der hBSCs. Darüber hinaus besitzen die hBSCs die Fähigkeit, stimulusabhängig Somatostatin zu exprimieren und zu sezernieren. Somit ist es erstmals gelungen, humane adulte Stammzellen/Progenitorzellen mit neuroendokrinen Eigenschaften zu isolieren. Zusammenfassend ist es in der vorliegenden Arbeit gelungen, eine Methode zu etablieren, mittels derer eine neue Population von humanen multipotenten Stammzellen aus der Haarfollikelregion in Langzeitkultur expandiert werden konnte. Die Plastizität der hBSCs und insbesondere die Differenzierung in reife endokrine Zellen muss in weiteren Studien untersucht werden.

Der akute Effekt einer einmaligen hohen Dosis von Anthrachinonen und diphenolischen Laxantien auf den Gehalt der Neurotransmitter VIP, Somatostatin und Substanz P des enterischen Nervensystems wurde in dieser Studie Untersucht. 450 weibliche Wistar-Ratten wurden 15 Gruppen zu je 30 Tieren randomisiert; sie erhielten eine einmalige Gabe entweder des Lösungsmittels (Kontrolltiere) oder einer hohen Dosis von Sennosiden, Danthron, Bisacodyl und Natriumpicosulphat. Zwei bzw. 6, bzw. 18 Stunden nach der Laxantieneinnahme wurde das Kolon den Tieren in Narkose entfernt. Nachdem die Darmsegmente, Colon ascendens und Colon descendens, entnommen wurden, erfolgte eine Trennung der drei Gewebsschichten Mukosa, Submukosa und Muskularis externa mittels Präparation. Nach Extraktion, Kochen und anschließender Homogenisierung in Essigsäure der jeweiligen Gewebsschichten ließ sich der Gehalt der Neurotransmitter VIP, Somatostatin und Substanz P mittels validierter Radioimmunassays bestimmen. Zwei Stunden nach der hochdosierten Gabe von Anthrachinonen und diphenolischen Laxantien fand keine Veränderung der Neurotransmittergehalte verglichen mit den Kontrollgruppen statt. Sechs Stunden nach Gabe von den diphenolischen Laxantien (Bisacodyl und Natriumpicosulphat) ließ sich eine signifikante Erhöhung des inhibitorischen Neurotransmitters Somatostatin in der Mukosa des Colon ascendens und in der Muskularis externa des Colon ascendens und Colon descendens nachweisen. Die einmalige hochdosierte Gabe von Natriumpicosulphat führte zusätzlich zu einer signifikanten Erhöhung des exzitatorischen Neurotransmitters Substanz P in der Submukosa des Colon ascendens. Die Applikation von Anthrachinonen (Sennoside und Danthron) ließ den Gehalt der Neurotransmitter unbeinflusst. Achtzehn Stunden nach Verabreichung der diphenolischen Laxantien zeigte sich eine signifikante Reduktion von VIP in der Muskularis externa des Colon descendens. Nach Applikation von Sennosiden kam es zu einer signifikante Reduktion von Somatostatin in der Submukosa des Colon descendens; die Gabe von Danthron führte zu einer signifikante Reduktion von VIP in der Muskularis externa des Colon descendens. Der Substanz P-Gehalt blieb unbeeinflusst. Daraus lässt sich folgern, dass eine einmalige hochdosierte Behandlung mit Anthrachinonen und diphenolischen Laxantien vorübergehend den Gehalt des inhibitorischen Neurotransmitters Somatostatin und des exzitatorischen Neuroransmitters Substanz P zu erhöhen, letztendlich jedoch den Gehalt der inhibitorischen Neurotransmitter VIP und Somatostatin zu vermindern vermag. Dies könnte Ausdruck einer toxischen Wirkung oder aber eines pharmakologischen Einflusses der Laxantien auf das enterische Nervensystem sein. Für letzteres spricht die fehlende Beeinflussbarkeit des exzitatorischen Neurotransmitters Substanz P; die Reduktion der inhibitorischen Neurotransmitter VIP und Somatostatin könnte durch eine verminderte Synthese oder durch einen vermehrten Abbau bedingt sein. Die kurzfristige Erhöhung der Neurotransmitter Somatostatin und Substanz P 6 Stunden nach Gabe diphenolischer Laxantien im Gegensatz zu den Anthrachinonen könnte Ausdruck eines unterschiedlichen Wirkungsmechanismus der beiden untersuchten Laxantiengruppen (Anthrachinone und diphenolische Laxantien) sein, die beide als antiabsorptiv, sekretagog und prokinetisch klassifiziert werden.

Ghrelin ist der natürliche Ligand des wachstumshormon-sekretagogen (GHS)-Rezeptors (Kojima, 1999). Es stimuliert die Wachstumshormon (GH)-Ausschüttung an der Hypophyse und wirkt appetitsteigernd. Bisherige schlafendokrinologische Untersuchungen zeigen, dass die Hormone wachstumshormon-freisetzendes-Hormon (GHRH), Somatostatin, corticotropin-freisetzendes Hormon (CRH) und Cortisol in die Schlafregulation involviert sind. Auch synthetische Wachstumshormon-Sekretagoge (GHS) modulieren beim Menschen den Schlaf und beeinflussen die nächtliche hormonellen Sekretion. Ziel dieser Arbeit war es, die Effekte von Ghrelin auf das Schlaf-EEG und die nächtliche Hormonsekretion von GH, ACTH, Cortisol, Prolaktin und Leptin bei jungen gesunden Männern zu untersuchen. Nach Gabe von 4 x 50 µg Ghrelin iv. zu Beginn der Nacht fand sich ein signifikanter Anstieg des Tiefschlafs im Schlaf-EEG und der assoziierten nächtlichen GH-, Cortisol- und Prolaktin-Sekretion. Die Leptinspiegel waren nicht signifikant verändert. Diese Arbeit konnte zeigen, dass exogen appliziertes Ghrelin signifikante Wirkungen auf den humanen Schlaf und die schlafassoziierte Hormonsekretion ausübt. Anhand der Ergebnisse ist davon auszugehen, dass Ghrelin nicht nur auf die GH-Sekretion, das Appetitverhalten oder das Gewicht Einfluss nehmen kann, sondern eigene endogen-schlafmodulierende Effekte ausübt und bei jungen gesunden Männern als tiefschlaffördernder Faktor angesehen werden kann. Weiterhin bewirkt Ghrelin einen deutlichen Effekt auf die somatotrophe und corticotrophe Hormonsekretion, indem es die physiologischen Sekretionsmuster von GH und Cortisol stimuliert und intensiviert. Bei Betrachtung der gegensätzlichen Wirkungen der einzelnen Hormone GHRH und CRH auf den Schlaf ist dabei bemerkenswert, dass Ghrelin die GH-sekretagogen und tiefschlaffördernden Effekte von GHRH und die Cortisol-sekretagogen Effekte von CRH vereint. Man kann postulieren, dass Ghrelin eine mögliche Schnittstelle des somatotrophen und des corticotrophen Systems darstellt.

Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited.

Intraduodenal (i.d.) application of bile or Na-taurodeoxycholate (TDC) dose dependently enhances basal exocrine pancreatic secretion. The hydrokinetic effect is mediated at least in part by secretin. This study should show, whether vasoactive intestinal polypeptide (VIP), a partial agonist of secretin, may also be involved in the mediation of the hydrokinetic effect. Furthermore, plasma concentrations of somatostatin-like immunoreactivity (SLI) were measured in order to check whether this counterregulating hormone is also released by bile and TDC. Twenty investigations were carried out on 10 fasting healthy volunteers provided with a double-lumen Dreiling tube. Bile and TDC were intraduodenally applied in doses of 2-6 g and 200-600 mg, respectively, at 65-min intervals. Plasma samples were withdrawn at defined intervals for radioimmunological determination of VIP and SLI. Duodenal juice was collected in 10-min fractions and analyzed for volume, pH, bicarbonate, lipase, trypsin, and amylase. I.d. application of bile or TDC dose dependently stimulated hydrokinetic and ecbolic pancreatic secretion. Bile exerted a slightly stronger effect than TDC. Pancreatic response was simultaneously accompanied by a significant increase of plasma VIP and SLI concentrations. The effect of bile on integrated plasma VIP and SLI concentrations seems to be dose dependent; the effect of TDC on integrated SLI, too. For the increase of integrated plasma VIP concentrations after TDC no dose-response relation could be established. We conclude that VIP may be a further mediator of bile-induced volume and bicarbonate secretion. The release of plasma SLI indicates that inhibitory mechanisms concomitantly are triggered by i.d. bile and TDC, as already shown during digestion for the intestinal phase of pancreatic secretion.

Wed, 1 Jan 1992 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6154/1/6154.pdf Lehnert, Peter; Fiedler, F.; Riepl, Rudolf L.

Sun, 1 Jan 1989 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7964/1/7964.pdf Goebel, Frank-Detlef; Matuschke, A.; Heinrich, B.; Bogner, Johannes R.; Kochen, M. M.; Zoller, W. G.; Füeßl, H. S. dd

This paper presents the first case of extensive, diffuse, somatostatin- immunoreactive D-cell hyperplasia in the human stomach and duodenum. It occurred in a 37-yr-old woman, who showed clinical signs of dwarfism, obesity, dryness of the mouth, and goiter. The density of the distribution of D cells was increased 39-fold in the stomach fundus, 23- fold in the proximal antrum, 25-fold in the distal antrum, and 31-fold in the upper duodenum in comparison with normal values. At the same time, the gastrin-immunoreactive cells were increased 2.3-fold in the antrum. Although the range in size of the D cells was within normal limits in all regions examined, the G cells showed pronounced hypertrophy of up to 127%. A possible relationship between the immuno- histochemical findings and the clinical picture is discussed.

Sat, 1 Jan 1977 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9248/1/9248.pdf Scriba, Peter Christian; Ziegler, R.; Landgraf, R.; Müller, O. A.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.17.047159v1?rss=1 Authors: Shin, S., Huang, S. Abstract: Disrupted interneurons have been extensively described in brain tissues from individuals with autism spectrum disorder (ASD) and animal models for ASD. However, the contribution of aberrant interneurons to autism-related behavioral phenotypes is not well understood. We examined ASD-related behaviors in mice with conditional Pten knockout in parvalbumin (PV)-expressing and somatostatin (Sst)-expressing neurons, two prominent subtypes of inhibitory neurons. We found that mice with deletion of Pten in either PV-neurons or Sst-neurons displayed social deficits, repetitive behaviors and impaired motor coordination/learning. In addition, mice with one copy of Pten deletion in PV-neurons exhibited hyperlocomotion in novel open fields. We also examined anxiety behaviors and found that mice with Pten deletion in Sst-neurons displayed anxiety-like behaviors, while mice with Pten deletion in PV-neurons exhibited anxiolytic-like behaviors. These behavioral assessments demonstrate that Pten knockout in the subtype of inhibitory neurons sufficiently gives rise to ASD-core behaviors, providing evidence that both PV- and Sst-neurons may play a critical role in ASD symptoms. Copy rights belong to original authors. Visit the link for more info

Optimizing Care in GEP-NET: Are All Somatostatin Analogues Created Equal?