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Author: Gregory Scott Parks
Publisher:
ISBN: 9781267430694
Category :
Languages : en
Pages : 159
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Book Description
Melanin-Concentrating Hormone, MCH, is hypothalamic neuropeptide that is expressed almost exclusively in the lateral hypothalamus and zona incerta. MCH activates two G protein-coupled receptors (GPCRs), MCHR1 and MCHR2, but only MCHR1 is expressed in rodents. It is well established that MCH regulates feeding and metabolism, but more recently it has been demonstrated to be involved in a wide range of other physiological functions such as reward, endocrine signaling, and the regulation of emotional state. While the physiological functions and downstream effects of MCH have been extensively investigated, relatively little is known about how the MCH system is controlled and regulated. In order to gain insight into how activity of MCH neurons is controlled, we have identified eleven neuropeptide receptors which are expressed by a significant amount of MCH neurons. Of these, six are entirely novel and have never been described or hypothesized to interact with the MCH system. These findings strongly suggest that these neuropeptide receptors represent novel circuits which function to regulate the MCH system. Several of these receptors have been demonstrated to regulate similar physiological functions as the MCH, indicating that they may exert their effects at least partially by modulating activity of MCH neurons. We have discovered and characterized an entirely novel circuit which regulates the MCH system. Most MCH neurons were found to express the histamine 3 receptor (H3R). Using cre-lox technology, we generated a novel reporter line to aid identification of MCH neurons for functional analysis of this circuit. Histamine was found to inhibit MCH neurons in hypothalamic slices, an effect which persisted in the presence of TTX, indicating that it acts on postsynaptic H3R. This effect was entirely blocked by a H3R antagonist and mimicked by a selective H3R agonist, indicating that histaminergic inhibition of MCH neurons is entirely mediated by H3R. Finally, we have discovered that mice lacking MCHR1 are highly resistant to several types of chemically induced seizures. This finding strongly suggests that the MCH system may be involved in regulating seizure threshold. Most strikingly, MCHR1 were found to be extremely resistant to pilocarpine induced seizures, a model for temporal lobe epilepsy, suggesting that the MCH system may be particularly important for these types of seizures. Taken together, this indicates that the MCH system may modulate susceptibility to seizures and that MCHR1 antagonists warrant investigation for potential anticonvulsant activity.
Author: Gregory Scott Parks
Publisher:
ISBN: 9781267430694
Category :
Languages : en
Pages : 159
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Book Description
Melanin-Concentrating Hormone, MCH, is hypothalamic neuropeptide that is expressed almost exclusively in the lateral hypothalamus and zona incerta. MCH activates two G protein-coupled receptors (GPCRs), MCHR1 and MCHR2, but only MCHR1 is expressed in rodents. It is well established that MCH regulates feeding and metabolism, but more recently it has been demonstrated to be involved in a wide range of other physiological functions such as reward, endocrine signaling, and the regulation of emotional state. While the physiological functions and downstream effects of MCH have been extensively investigated, relatively little is known about how the MCH system is controlled and regulated. In order to gain insight into how activity of MCH neurons is controlled, we have identified eleven neuropeptide receptors which are expressed by a significant amount of MCH neurons. Of these, six are entirely novel and have never been described or hypothesized to interact with the MCH system. These findings strongly suggest that these neuropeptide receptors represent novel circuits which function to regulate the MCH system. Several of these receptors have been demonstrated to regulate similar physiological functions as the MCH, indicating that they may exert their effects at least partially by modulating activity of MCH neurons. We have discovered and characterized an entirely novel circuit which regulates the MCH system. Most MCH neurons were found to express the histamine 3 receptor (H3R). Using cre-lox technology, we generated a novel reporter line to aid identification of MCH neurons for functional analysis of this circuit. Histamine was found to inhibit MCH neurons in hypothalamic slices, an effect which persisted in the presence of TTX, indicating that it acts on postsynaptic H3R. This effect was entirely blocked by a H3R antagonist and mimicked by a selective H3R agonist, indicating that histaminergic inhibition of MCH neurons is entirely mediated by H3R. Finally, we have discovered that mice lacking MCHR1 are highly resistant to several types of chemically induced seizures. This finding strongly suggests that the MCH system may be involved in regulating seizure threshold. Most strikingly, MCHR1 were found to be extremely resistant to pilocarpine induced seizures, a model for temporal lobe epilepsy, suggesting that the MCH system may be particularly important for these types of seizures. Taken together, this indicates that the MCH system may modulate susceptibility to seizures and that MCHR1 antagonists warrant investigation for potential anticonvulsant activity.
Author: S. R. Pandi-Perumal
Publisher: Springer
ISBN: 3319757652
Category : Science
Languages : en
Pages : 236
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Book Description
This book offers a compilation of papers on the role of melanin-concentrating hormone (MCH) in sleep, sleep disorders and neuroendocrine functions. Leading experts in sleep medicine, psychiatry and neuroendocrinology provide a broad perspective on the field, from the anatomical structure and physiology of the MCH system to the connection with other systems influencing sleep and diseases like anxiety and depression. The potential of MCHR-1 antagonists as anxiolytic/antidepressant drugs is also reviewed. The book will represent an interdisciplinary guide for sleep disorder specialists, sleep researchers, psychiatrists, neurologists, psychologists, and behavioral sleep medicine specialists.
Author: Eyitemi Joseph Egwuenu
Publisher:
ISBN:
Category : Cardiopulmonary system
Languages : en
Pages : 241
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Book Description
Author: Ningjing Li
Publisher:
ISBN:
Category :
Languages : en
Pages : 300
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Book Description
The lateral hypothalamus is a brain region involved in the regulation of feeding, glucose homeostasis, sleep/wake cycle, and autonomic nervous system (ANS). Melanin concentrating hormone (MCH) containing neurons, located in the lateral hypothalamus, project widely throughout the central nervous system, including the brain regions that are involved in central chemoreception, food intake, and sleep. These neurons also have multisynaptic connections with the phrenic motoneurons and the ANS. My overall hypothesis is that the lateral hypothalamus is a central chemoreceptor site and hypothalamic MCH neurons play a role in central chemoreception, cardiovascular control, and energy balance. Electroencephalogram (EEG) and electromyogram (EMG) electrodes were surgically implanted to record vigilance states. Arterial catheters were implanted for blood pressure and heart rate recordings. Whole body plethysmography was used to measure ventilation and metabolic rate while breathing in room air of 5% CO2. In the first series of experiments, reverse-microdialysis was used to focally deliver artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO2 to perifornical-lateral hypothalamic area (PF-LHA) in conscious rats while breathing in room air. In the second series of experiments, siRNA was used to knock down the expression of the MCH precursor gene (pMCH) to lower the levels of MCH in the brain. In the third series of experiments, acute central injection of MCH was applied in the third ventricle. Focal acidification in the PF-LHA caused an increase in ventilation only during quiet wakefulness, suggesting that the PF-LHA functions as a central chemoreceptor site and does so in a vigilance-state dependent manner. Knockdown of the pMCH expression resulted in an increase in the ventilatory response to 5% CO2 only during quiet wakefulness, accompanied by an increased metabolic rate, a reduced body weight and glucose level, as well as a disturbed sleep-wake cycle. Central injection of MCH induced food and water intake and lowered metabolic rate and blood pressure. Overall, these results indicate that hypothalamic MCH neurons are involved in central chemoreception in wakefulness, and suggest that disturbance of their function could contribute to obesity and obesity-related breathing and metabolic disorders.
Author: Sonia Jego
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
"Sleep is a fundamental physiological process and sleep-like states have been described in nearly every animal studied to date. Despite the existence of distinct sleep-wake states, our understanding of the mechanism of sleep regulation remains incomplete. The present work focused on a particular hypothalamic neuronal population which expresses melanin-concentrating hormone (MCH). The MCH peptide is thought to have a role in the promotion of sleep. However, all of the evidence supporting a functional role for the MCH system in sleep stems from in vitro and in vivo techniques that have spatial and temporal limitations and involve possible compensatory mechanisms. The present work aimed at clarifying the action of MCH neurons and their co-expressed neurotransmitters on sleep.In our first study, we used optogenetic tools in newly-generated Tg(Pmch-Cre) mice and found that acute optical activation of MCH neurons at the onset of REM sleep extended REM sleep duration whereas MCH neuronal stimulation at NREM sleep onset promoted transition from NREM to REM sleep. In contrast, acute silencing of MCH neurons reduced the frequency and amplitude of the hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory post-synaptic currents in wake-promoting neurons of the tuberomammillary nucleus (TMN), while in vivo activation of MCH neuron terminals in the TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain, while their inhibition induced a NREM-to-REM sleep transitional state.Our second study investigated the role of MCH peptide and GABA transmitter, which are thought to be both released by MCH neurons, during acute and semi-chronic optogenetic activation of MCH cells. We used newly-generated mice along with administration of MCH-R1 antagonist SNAP 7941. Our study revealed that the absence of Vesicular GABA Transporter (VGAT) in MCH neurons raises REM sleep mean duration closer to a ceiling value in control condition, masking the REM sleep promoting effect in acute stimulation. Semi-chronic activation of MCH neurons revealed that MCH peptide likely mediates the NREM sleep promoting effect whereas REM sleep promoting effect might involve additional neurotransmitters beside GABA neurotransmission. Together, our results suggest that GABA produced by MCH neurons is playing a crucial role in the basal control of REM sleep. Importantly, these results have confirmed that the mode of MCH activation (acute vs. semi-chronic) has a different effect on sleep, possibly due to the release of various neurotransmitters acting on various targets with different timescales. In the third study, we investigated the effect of pharmacogenetic activation of MCH neurons in the lateral hypothalamus and found that their activation during the resting period (i.e., light period) specifically increased REM sleep whereas a similar activation paradigm during the active period (i.e., dark period) enhanced wakefulness and possibly arousal. These results suggest that subpopulations of MCH neurons exist, and that their modulation of behavior, including sleep, depends on the circadian phase and the physiological and homeostatic need of the animal.Collectively, our results causally demonstrated that MCH neurons are involved in REM sleep regulation, at least during the light phase. Acute activation of MCH neurons significantly promotes REM sleep although this effect is not dependent on MCH peptide release, whereas GABA from MCH neurons is possibly involved in the regulation of basal REM sleep. Our results further suggest that MCH peptide is implicated in the modulation of NREM sleep following semi-chronic activation of MCH soma, consistent with the slow mechanism of action of peptides in the brain. " --
Author: Sangdun Choi
Publisher: Springer
ISBN: 9781441904607
Category : Medical
Languages : en
Pages : 0
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Book Description
Biological processes are driven by complex systems of functionally interacting signaling molecules. Thus, understanding signaling molecules is essential to explain normal or pathological biological phenomena. A large body of clinical and experimental data has been accumulated over these years, albeit in fragmented state. Hence, systems biological approaches concomitant with the understanding of each molecule are ideal to delineate signaling networks/pathways involved in the biologically important processes. The control of these signaling pathways will enrich our healthier life. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities. This encyclopedia presents 350 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike During past years, there were multiple databases to gather this information briefly and very partially. Amidst the excitement of these findings, one of the great scientific tasks of the coming century is to bring all the useful information into a place. Such an approach is arduous but at the end will infuse the lacunas and considerably be a streamline in the understanding of vibrant signaling networks. Based on this easy-approach, we can build up more complicated biological systems.
Author: Mitchell G. Miglis
Publisher: Academic Press
ISBN: 0128041129
Category : Science
Languages : en
Pages : 270
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Book Description
Sleep and Neurologic Disease reviews how common neurologic illnesses, such as Parkinson's Disease and Alzheimer's dementia impact sleep. In addition, the book discusses how common primary sleep disorders influence neurologic diseases, such as the relationship between obstructive sleep apnea and stroke, as well as their association with various primary headache disorders and epilepsy syndromes. The utilization of sleep technology, such as polysomnography, multiple sleep latency testing, actigraphy, laboratory and CSF testing is also covered. The book is written for the practicing neurologist, sleep physician, neuroscientist, and epidemiologist studying sleep. - Reviews how common neurological illnesses impact sleep and the impact sleep disorders have on neurologic disease - Up-to-date, comprehensive overview written for practicing neurologists, sleep physicians, neuroscientists, and epidemiologists - Includes informative discussions on sleep physiology, circadian rhythms, sleep and stroke, and treatment options for neurologists
Author: Valery Grinevich
Publisher: Springer
ISBN: 9783030866327
Category : Medical
Languages : en
Pages : 0
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Book Description
In this book, experts in the field provide comprehensive descriptions of the neuroanatomy of the hypothalamic neuroendocrine systems. The book begins with an extensive discussion on the structural components of the neuroendocrine systems. The reader will be introduced to the anatomy and biology of the hypothalamus and the pituitary. The human hypothalamus is presented in particular detail using state-of-the-art imaging techniques. In the next section, the neuroanatomy of traditional hypothalamo-hypophyseal systems is highlighted, with chapters describing magnocellular neuroendocrine cells and discussing the respective types of hypothalamic neurons that regulate various pituitary hormones. Following this detailed structural and anatomical description of the neuroendocrine system, the book’s final section focuses on the hypothalamic control of neuroendocrine functions. This includes the control of circadian rhythm, metabolism and appetite via specific peptidergic circuits. This book provides essential information on the neuroanatomy and control of neuroendocrine systems, addresses cutting-edge research questions posed by recent advances in the development of potent neuroanatomical tools, and highlights the latest technologies used in neuroendocrinology research, making it a valuable reference guide for students, trainees and established researchers alike. This is the twelfth volume in the International Neuroendocrine Federation (INF) Masterclass in Neuroendocrinology series, which aims to illustrate the highest standards and to encourage the use of the latest technologies in basic and clinical research and hopes to provide inspiration for further exploration into the exciting field of neuroendocrinology. Chapter 12 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com
Author: Robert A. McArthur
Publisher: Academic Press
ISBN: 0080920411
Category : Science
Languages : en
Pages : 1367
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Book Description
Animal and Translational Models for CNS Drug Discovery combines the experience of academic, clinical and pharmaceutical neuroscientists in a unique collaborative approach to provide a greater understanding of the relevance of animal models of neuropsychiatric disorders and their role as translational tools for the discovery of CNS drugs being developed for the treatment of these disorders. The focus of this three-volume series of essays is to present a consensual picture of the translational value of animal models from leading experts actively involved in the use of animal models for understanding fundamental neurobiology of CNS disorders and the application of this knowledge to CNS drug discovery, and clinical investigators involved in clinical trials, drug development and eventual registration of novel pharmaceuticals. Each volume of the Animal and Translational Models for CNS Drug Discovery series is dedicated to the development and use of animal models in key therapeutic areas in psychiatric, neurologic and reward deficit disorders. Each volume has introductory chapters expressing the view of the role and relevance of animal models for CNS drug discovery and development from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in relevant therapeutic areas and discusses the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. The aim of this series of volumes on Animal and Translational Models for CNS Drug Discovery is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery. - Provides clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery process - Critical evaluation of animal and translational models improving transition from drug discovery and clinical development - Emphasizes what results mean to the overall drug discovery process - Explores issues in clinical trial design and conductance in each therapeutic area - Each volume is available for purchase individually.
Author: Andrzej T. Slominski
Publisher: Springer Science & Business Media
ISBN: 3642196837
Category : Medical
Languages : en
Pages : 128
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Book Description
The skin, the body’s largest organ, is strategically located at the interface with the external environment where it detects, integrates and responds to a diverse range of stressors, including solar radiation. It has already been established that the skin is an important peripheral neuroendocrine-immune organ that is closely networked with central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides and hormones, production which is stimulated by ultraviolet radiation (UVR), biological factors (infectious and non-infectious) and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, b-endorphin or MSH peptides, thyroid stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones, as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7-δ steroids), secosteroids, opioids and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as the hypothalamic pituitary adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid and endocannabinoid systems. Disruptions of these axes or of communication between them may lead to skin and/or systemic diseases. These local neuroendocrine networks also serve to limit the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve endings to alert the brain to changes in the epidermal or dermal environments, or alternatively to activate other coordinating centers by direct (spinal cord) neurotransmission without brain involvement. Furthermore, rapid and reciprocal communications between epidermal and dermal and adnexal compartments are also mediated by neurotransmission including antidromic modes of conduction. Lastly, skin cells and the skin as an organ coordinate and/or regulate not only peripheral but also global homeostasis.
