Hypothalamus

About: Hypothalamus is a research topic. Over the lifetime, 22301 publications have been published within this topic receiving 1085925 citations.

Agouti-related peptide-expressing neurons are mandatory for feeding.

Abstract: Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.

Histamine-containing neurons in the rat hypothalamus.

Abstract: A specific antiserum against histamine was produced in rabbits, and an immunohistochemical study of histamine-containing cells was carried out in rat brain. The antiserum bound histamine in a standard radioimmunoassay and stained mast cells located in various rat and guinea pig tissues. Enterochromaffin-like cells in the stomach and neurons in the posterior hypothalamic area could be detected with this antiserum. The staining was highly specific and was not abolished by preabsorption with histidine, histidine-containing peptides, serotonin, or catecholamines, whereas preabsorption with histamine completely abolished the staining. Immunoglobulins of this antiserum purified by affinity chromatography stained the same cells as did the crude antiserum, whereas the serum fraction, which was not absorbed by histamine-affinity ligand, failed to stain any neuron. Histamine-immunoreactive neuronal cell bodies were found only in the hypothalamic and premammillary areas of colchicine-treated rats. The largest group of cells was seen in the caudal magnocellular nucleus and medially on the dorsal and ventral aspects of the ventral premammillary nucleus. Immunoreactive nerve fibers, but no cell bodies, were detected in other parts of the brain. Histamine-immunoreactive mast cells were found in the median eminence and pituitary gland. The results suggest that histamine-containing neurons are located only in a small area of the posterior hypothalamus, and these cells are probably the source of ascending and descending fibers detected in other brain areas.

Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice

Abstract: Leptin resistance in diet-induced obese (DIO) mice is characterized by elevated serum leptin and a decreased response to exogenous leptin and is caused by unknown defects in the central nervous system. Leptin normally acts on several brain nuclei, but a detailed description of leptin resistance within individual brain regions has not been reported. We first mapped leptin-responsive cells in brains from DIO mice using phospho-signal transducer and activator of transcription (P-STAT3) immunohistochemistry. After 16 wk of high-fat-diet feeding, leptin-activated P-STAT3 staining within the arcuate nucleus (ARC) was dramatically decreased. In contrast, other hypothalamic and extrahypothalamic nuclei remained leptin sensitive. Reduced leptin-induced P-STAT3 in the ARC could also be detected after 4 wk and as early as 6 d of a high-fat diet. To examine potential mechanisms for leptin-resistant STAT3 activation in the ARC of DIO mice, we measured mRNA levels of candidate signaling molecules in the leptin receptor-STAT3 pathway. We found that the level of suppressor of cytokine signaling 3 (SOCS-3), an inhibitor of leptin signaling, is specifically increased in the ARC of DIO mice. The study suggests that the ARC is selectively leptin resistant in DIO mice and that this may be caused by elevated suppressor of cytokine signaling 3 in this hypothalamic nucleus. Defects in leptin action in the ARC may play a role in the pathogenesis of leptin-resistant obesity.

Functional Cross-Talk Between the Hypothalamic-Pituitary-Gonadal and -Adrenal Axes

Abstract: Under normal conditions, the adrenal glucocorticoids, the endproduct of the hypothalamic-pituitary-adrenal (HPA) axis, provide a frontline of defence against threats to homeostasis (i.e. stress). On the other hand, chronic HPA drive and glucocorticoid hypersecretion have been implicated in the pathogenesis of several forms of systemic, neurodegenerative and affective disorders. The HPA axis is subject to gonadal influence, indicated by sex differences in basal and stress HPA function and neuropathologies associated with HPA dysfunction. Functional cross-talk between the gonadal and adrenal axes is due in large part to the interactive effects of sex steroids and glucocorticoids, explaining perhaps why several disease states linked to stress are sex-dependent. Realizing the interactive nature by which the hypothalamic-pituitary-gonadal and HPA systems operate, however, has made it difficult to model how these hormones act in the brain. Manipulation of one endocrine system is not without effects on the other. Simultaneous manipulation and assessment of both endocrine systems can overcome this problem. This dual approach in the male rat reveals that testosterone can act and interact on different aspects of basal and stress HPA function. Basal adrenocorticotropic hormone (ACTH) release is regulated by testosterone-dependent effects on arginine vasopressin synthesis, and corticosterone-dependent effects on corticotropin-releasing hormone (CRH) synthesis in the paraventricular nucleus (PVN) of the hypothalamus. In contrast, testosterone and corticosterone interact on stress-induced ACTH release and drive to the PVN motor neurones. Candidate structures mediating this interaction include several testosterone-sensitive afferents to the HPA axis, including the medial preoptic area, central and medial amygdala and bed nuclei of the stria terminalis. All of these relay homeostatic information and integrate reproductive and social behaviour. Because these modalities are affected by stress in humans, a dual systems approach holds great promise in establishing further links between the neuroendocrinology of stress and the central bases of sex-dependent disorders, including psychiatric, cardiovascular and metabolic disease.