Brain hypothalamus, nucleus

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

The paraventricular nucleus in the hypothalamus is located adjacent to the third ventricle and has been identified as a satiety center. Neurons in the paraventricular nucleus produce neuropeptides which inhibit feeding when injected into the brain (thyrotropinreleasing hormone (TRH), corticotropin-releasing hormone (CRH), oxytocin). 

High amounts of somatostatin are found in the CNS, the peripheral nervous system, the gut and the endocrine pancreas whereas the kidneys, adrenals, thyroid, submandibular glands, prostate and placenta produce rather low amounts. In particular, the hypothalamus, all limbic structures, the deeper layers of the cerebral cortex, the striatum, the periaqueductal central grey and all levels of the major sensoty pathway are brain areas that are especially rich in somatostatin. Eighty percent of the somatostatin immunoreactivity in the hypothalamus is found in cells of the anterior periventricular nucleus (Fig. 1, [1]). The gut 5 cells of the mucosa and neurons, which are intrinsic to the submucous and... 

Obviously, regulation of food intake depends on many neurotransmitters and hormones but this final section will outline the role played by central 5-HT transmission in this process. It had been the belief for some time that increased 5-HT transmission in the brain reduces food intake (Blundell 1977) and this certainly explains the satiety in rats that follows infusion of 5-HT into the paraventricular nucleus (PVN) of the hypothalamus. However, recent studies using microdialysis have found that 5-HT efflux in the lateral hypothalamus is itself increased by food intake, suggesting the existence of a feedback control system. In fact, because the increase in 5-HT efflux is greater in genetically obese rats than in their lean counterparts, it has been proposed that there is a deficiency in the 5-HT inhibition of food intake in obesity. 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Figure 6.2 The location and distribution of the histamine-containing neurons in the brain. These neurons are localized in the tuberomammiUaiy nucleus within the posterior hypothalamus and send projections throughout the brain. Abbreviations Hi, hippocampus Hy, hypothalamus IC, inferior colliculus OB, olfactory bulb SC, superior colliculus SI, substantia innominata St, striatum TH, thalamus TMN, tuberomammillary nucleus. Adapted from Watanabe Yanai (2001).

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

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