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The Psychiatric Clinics of North America Dec 2015Cortical electroencephalographic activity arises from corticothalamocortical interactions, modulated by wake-promoting monoaminergic and cholinergic input. These... (Review)
Review
Cortical electroencephalographic activity arises from corticothalamocortical interactions, modulated by wake-promoting monoaminergic and cholinergic input. These wake-promoting systems are regulated by hypothalamic hypocretin/orexins, while GABAergic sleep-promoting nuclei are found in the preoptic area, brainstem and lateral hypothalamus. Although pontine acetylcholine is critical for REM sleep, hypothalamic melanin-concentrating hormone/GABAergic cells may "gate" REM sleep. Daily sleep-wake rhythms arise from interactions between a hypothalamic circadian pacemaker and a sleep homeostat whose anatomical locus has yet to be conclusively defined. Control of sleep and wakefulness involves multiple systems, each of which presents vulnerability to sleep/wake dysfunction that may predispose to physical and/or neuropsychiatric disorders.
Topics: Biogenic Monoamines; Brain; Cholinergic Neurons; Circadian Clocks; GABAergic Neurons; Humans; Hypothalamic Hormones; Melanins; Neural Pathways; Orexins; Pituitary Hormones; Sleep; Wakefulness
PubMed: 26600100
DOI: 10.1016/j.psc.2015.07.002 -
Seminars in Reproductive Medicine Mar 2019The hypothalamic hormone kisspeptin (encoded by the KISS1/kiss1 gene) is the master regulator of the reproductive axis with its role in controlling gonadotrophin hormone... (Review)
Review
The hypothalamic hormone kisspeptin (encoded by the KISS1/kiss1 gene) is the master regulator of the reproductive axis with its role in controlling gonadotrophin hormone secretion now well characterized. However, identification of kisspeptin and its cognate receptor expression within the amygdala, a key limbic brain region whose functions contribute to a broad range of physiological and behavioral processes, has heightened interest concerning kisspeptins' role in the broader aspects of reproductive physiology. In this review, we detail the important developments and key studies examining the emerging functions of this kisspeptin population. These studies provide novel advances in our understanding of the mechanisms controlling reproductive neuroendocrinology by defining the crucial role of the amygdala kisspeptin system in modulating pubertal timing, reproductive hormone secretion, and pulsatility, as well as its influence in governing-related behaviors. To this end, the role of the amygdala kisspeptin system in integrating reproductive hormone secretion with behavior sheds new light onto the potential use of kisspeptin-based therapeutics for reproductive and related psychosexual disorders.
Topics: Amygdala; Animals; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Male; Puberty; Reproductive Behavior; Signal Transduction
PubMed: 31847026
DOI: 10.1055/s-0039-3400462 -
Endocrinology Dec 2022The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a... (Review)
Review
The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a crucial element in homeostasis maintenance, and regulates the release of growth hormone from the anterior pituitary gland. Accumulating evidence suggests that this neuropeptide can also promote malignancies, as well as inflammation. Our review is focused on the role of that 44 - amino acid peptide (GHRH) and its antagonists in inflammation and vascular function, summarizing recent findings in the corresponding field. Preclinical studies demonstrate the protective role of GHRH antagonists against endothelial barrier dysfunction, suggesting that the development of those peptides may lead to new therapies against pathologies related to vascular remodeling (eg, sepsis, acute respiratory distress syndrome). Targeted therapies for those diseases do not exist.
Topics: Humans; Growth Hormone-Releasing Hormone; Growth Hormone; Pituitary Gland, Anterior; Peptides; Inflammation; Receptors, Pituitary Hormone-Regulating Hormone
PubMed: 36503995
DOI: 10.1210/endocr/bqac209 -
Nature Communications Mar 2023The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating...
The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.
Topics: Rats; Male; Animals; Hypothalamic Hormones; Hypothalamus; Pituitary Hormones; Melanins; Hypothalamic Area, Lateral; Neurons
PubMed: 36990984
DOI: 10.1038/s41467-023-37344-9 -
Journal of Neuroendocrinology Jul 2021Prader-Willi Syndrome (PWS) is a rare and incurable congenital neurodevelopmental disorder, resulting from the absence of expression of a group of genes on the... (Review)
Review
Prader-Willi Syndrome (PWS) is a rare and incurable congenital neurodevelopmental disorder, resulting from the absence of expression of a group of genes on the paternally acquired chromosome 15q11-q13. Phenotypical characteristics of PWS include infantile hypotonia, short stature, incomplete pubertal development, hyperphagia and morbid obesity. Hypothalamic dysfunction in controlling body weight and food intake is a hallmark of PWS. Neuroimaging studies have demonstrated that PWS subjects have abnormal neurocircuitry engaged in the hedonic and physiological control of feeding behavior. This is translated into diminished production of hypothalamic effector peptides which are responsible for the coordination of energy homeostasis and satiety. So far, studies with animal models for PWS and with human post-mortem hypothalamic specimens demonstrated changes particularly in the infundibular and the paraventricular nuclei of the hypothalamus, both in orexigenic and anorexigenic neural populations. Moreover, many PWS patients have a severe endocrine dysfunction, e.g. central hypogonadism and/or growth hormone deficiency, which may contribute to the development of increased fat mass, especially if left untreated. Additionally, the role of non-neuronal cells, such as astrocytes and microglia in the hypothalamic dysregulation in PWS is yet to be determined. Notably, microglial activation is persistently present in non-genetic obesity. To what extent microglia, and other glial cells, are affected in PWS is poorly understood. The elucidation of the hypothalamic dysfunction in PWS could prove to be a key feature of rational therapeutic management in this syndrome. This review aims to examine the evidence for hypothalamic dysfunction, both at the neuropeptidergic and circuitry levels, and its correlation with the pathophysiology of PWS.
Topics: Animals; Humans; Hyperphagia; Hypogonadism; Hypothalamic Hormones; Hypothalamus; Nerve Net; Neuropeptides; Obesity; Prader-Willi Syndrome
PubMed: 34156126
DOI: 10.1111/jne.12994 -
International Journal of Molecular... Mar 2018The Hypothalamic-Pituitary-adrenal (HPA) axis describes a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal...
The Hypothalamic-Pituitary-adrenal (HPA) axis describes a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal gland.[...].
Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Feedback, Physiological; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 29587417
DOI: 10.3390/ijms19040986 -
Clinical Medicine (London, England) Mar 2023Adrenal insufficiency is the inadequate secretion of glucocorticoid and/or mineralocorticoid secretion from the adrenal cortex. Primary adrenal insufficiency is the...
Adrenal insufficiency is the inadequate secretion of glucocorticoid and/or mineralocorticoid secretion from the adrenal cortex. Primary adrenal insufficiency is the result of failure of the adrenal gland and secondary adrenal insufficiency is due to a lack of stimulation via pituitary adrenocorticotropic hormone or hypothalamic corticotropin-releasing hormone. Adrenal insufficiency may cause non-specific symptoms. Early detection and testing based on clinical suspicion may prevent subsequent presentation with adrenal crisis. Once identified, a low baseline cortisol (often <100 nmol/L) alongside raised adrenocorticotropic hormone (ACTH) can be enough to diagnose primary adrenal insufficiency. However, confirmatory testing can be done using the cosyntopin (Synacthen®) stimulation test or the insulin tolerance test, which is the gold standard for secondary adrenal insufficiency. The underlying cause of adrenal insufficiency can often be identified via a strategic approach to investigation. Adrenal crisis is a life-threatening medical emergency which must be treated immediately if there is strong clinical suspicion with fluids and corticosteroids otherwise can be fatal. Patients must be educated and empowered to take control of their own medical management.
Topics: Humans; Hydrocortisone; Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone
PubMed: 36958832
DOI: 10.7861/clinmed.2023-0067 -
Peptides Mar 2021Given the increased prevalence of obesity and its associated comorbidities, understanding the mechanisms through which the brain regulates energy balance is of critical... (Review)
Review
Given the increased prevalence of obesity and its associated comorbidities, understanding the mechanisms through which the brain regulates energy balance is of critical importance. The neuropeptide melanin-concentrating hormone (MCH) is produced in the lateral hypothalamic area and the adjacent incerto-hypothalamic area and promotes both food intake and energy conservation, overall contributing to body weight gain. Decades of research into this system has provided insight into the neural pathways and mechanisms (behavioral and neurobiological) through which MCH stimulates food intake. Recent technological advancements that allow for selective manipulation of MCH neuron activity have elucidated novel mechanisms of action for the hyperphagic effects of MCH, implicating neural "volume" transmission in the cerebrospinal fluid and sex-specific effects of MCH on food intake control as understudied areas for future investigation. Highlighted here are historical and recent findings that illuminate the neurobiological mechanisms through which MCH promotes food intake, including the identification of various specific neural signaling pathways and interactions with other peptide systems. We conclude with a framework that the hyperphagic effects of MCH signaling are predominantly mediated through enhancement of an "appetition" process in which early postoral prandial signals promote further caloric consumption.
Topics: Appetite; Eating; Energy Metabolism; Female; Humans; Hypothalamic Hormones; Hypothalamus; Male; Melanins; Neurons; Neuropeptides; Obesity; Pituitary Hormones; Signal Transduction
PubMed: 33370567
DOI: 10.1016/j.peptides.2020.170476 -
Frontiers of Neurology and Neuroscience 2021During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our... (Review)
Review
During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our understanding of brain structures causally involved in the regulation of sleep-wake cycles. Recent imaging technologies enable the functional mapping of cellular activity, from population down to single-cell resolution, across a broad repertoire of behaviors and physiological processes, including sleep-wake states. This chapter summarizes experimental evidence implicating hypocretins/orexins, melanin-concentrating hormone, and inhibitory neurons from the lateral hypothalamus (LH) in forming an intricate network involved in regulating sleep and metabolism, including feeding behaviors. It further confirms the dual sleep-metabolic functions of LH cells, and sheds light on a possible mechanism underlying brain plasticity during sleep and metabolic disorders.
Topics: Animals; Feeding Behavior; Humans; Hypothalamic Area, Lateral; Hypothalamic Hormones; Melanins; Nerve Net; Neurons; Orexins; Pituitary Hormones; Sleep
PubMed: 34052816
DOI: 10.1159/000514966 -
The Journal of Neuroscience : the... Jun 2023Corticotropin-releasing hormone (CRH) is a neuropeptide regulating neuroendocrine and autonomic function. CRH mRNA and protein levels in the hypothalamic paraventricular...
Corticotropin-releasing hormone (CRH) is a neuropeptide regulating neuroendocrine and autonomic function. CRH mRNA and protein levels in the hypothalamic paraventricular nucleus (PVN) are increased in primary hypertension. However, the role of CRH in elevated sympathetic outflow in primary hypertension remains unclear. CRHR1 proteins were distributed in retrogradely labeled PVN presympathetic neurons with an increased level in the PVN tissue in adult spontaneously hypertensive rats (SHRs) compared with age-matched male Wistar-Kyoto (WKY) rats. CRH induced a more significant increase in the firing rate of PVN-rostral ventrolateral medulla (RVLM) neurons and sympathoexcitatory response in SHRs than in WKY rats, an effect that was blocked by preapplication of NMDA receptors (NMDARs) antagonist AP5 and PSD-95 inhibitor, Tat-N-dimer. Blocking CRHRs with astressin or CRHR1 with NBI35965 significantly decreased the firing rate of PVN-RVLM output neurons and reduced arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in SHRs but not in WKY, whereas blocking CRHR2 with antisauvagine-30 did not. Furthermore, Immunocytochemistry staining revealed that CRHR1 colocalized with NMDARs in PVN presympathetic neurons. Blocking CRHRs significantly decreased the NMDA currents in labeled PVN neurons. PSD-95-bound CRHR1 and PSD-95-bound GluN2A in the PVN were increased in SHRs. These data suggested that the upregulation of CRHR1 in the PVN is critically involved in the hyperactivity of PVN presympathetic neurons and elevated sympathetic outflow in primary hypertension. Our study found that corticotropin-releasing hormone receptor (CRHR)1 protein levels were increased in the paraventricular nucleus (PVN), and CRHR1 interacts with NMDA receptors (NMDARs) through postsynaptic density protein (PSD)-95 in the PVN neurons in primary hypertension. The increased CRHR1 and CRHR1-NMDAR-PSD-95 complex in the PVN contribute to the hyperactivity of the PVN presympathetic neurons and elevated sympathetic vasomotor tone in hypertension in SHRs. Thus, the antagonism of CRHR1 decreases sympathetic outflow and blood pressure in hypertension. These findings determine a novel role of CRHR1 in elevated sympathetic vasomotor tone in hypertension, which is useful for developing novel therapeutics targeting CRHR1 to treat elevated sympathetic outflow in primary hypertension. The CRHR1 receptor antagonists, which are used to treat health consequences resulting from chronic stress, are candidates to treat primary hypertension.
Topics: Animals; Male; Rats; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Essential Hypertension; Hypertension; Paraventricular Hypothalamic Nucleus; Pituitary Hormone-Releasing Hormones; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, N-Methyl-D-Aspartate; Sympathetic Nervous System
PubMed: 37160364
DOI: 10.1523/JNEUROSCI.2343-22.2023