Hypothalamus

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

Estrogen receptor messenger ribonucleic acid in female rat brain during the estrous cycle: a comparison with ovariectomized females and intact males.

Abstract: Variations in levels of estrogen receptor mRNA were investigated in the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus throughout the phases of the female estrous cycle and compared with those in ovariectomized female and intact male rats. Female Wistar rats were killed during estrus, metestrus, diestrus, or proestrus or 72 h after ovariectomy as were a group of intact male rats. Brains were removed and frozen, and 20-microns cryostat sections were thaw-mounted onto slides and hybridized with a 35S-labeled antisense estrogen receptor probe. Section-mounted slides were processed, apposed to x-ray film, then dipped in liquid emulsion, and quantified. After exposure, estrogen receptor mRNA was detected in several brain regions, including the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus. Estrogen receptor mRNA levels in the medial preoptic nucleus were highest during estrus and metestrus, attenuated at diestrus, and low during proestrus. In contrast, the hybridization signal in the arcuate and ventromedial nuclei was low during estrus and then gradually increased throughout the cycle until it peaked during proestrus. Ovariectomized females exhibited an elevated level of estrogen receptor mRNA in all brain regions investigated. Hybridization signal in male medial preoptic nucleus and ventromedial nucleus was reduced compared with those in both intact and ovariectomized females. Estrogen receptor mRNA levels in the arcuate nucleus were similar to those in intact females, but less than those in ovariectomized animals. The results of these studies demonstrate that estrogen receptor mRNA levels are sexually dimorphic, vary during the estrous cycle, and increase after ovariectomy. Furthermore, these results indicate that the magnitude and direction of change observed during the estrous cycle are region specific and suggest that factors other than endogenous estrogen levels differentially modulate estrogen receptor mRNA expression in the hypothalamus.

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Abstract: Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: An in situ hybridization study

Abstract: The distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1-CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann glia cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies.

Hypothalamic effector neurons and extended circuitries activated in “neurogenic” stress: A comparison of footshock effects exerted acutely, chronically, and in animals with controlled glucocorticoid levels

Abstract: Immunolocalization of Fos protein was used to identify and characterize hypothalamic visceromotor populations responsive to acute and chronic intermittent footshock stress, and candidate afferent mediators of hypothalamic effects Exposure to a single 30 minute footshock session induced maximal Fos expression in the paraventricular hypothalamic nucleus (PVH) 2 hours after the challenge; activated cells corresponded principally to hypophysiotropic neurons expressing corticotropin-releasing factor, with secondary involvement of magnocellular oxytocinergic and autonomic-related projection neurons Extrahypothalamic cell groups activated in response to acute footshock included ones associated with the processing or modulation of somatosensory/nociceptive inputs, the limbic region of the telencephalon, and visceral sensory mechanisms Rats with constant corticosterone levels displayed enhanced footshock-induced Fos expression in the parvicellular compartment of the PVH, as well as in certain limbic and somatosensory cell groups, the locus coeruleus, but not in medullary catecholaminergic cell groups Animals subjected to chronic intermittent stress (2 sessions/day for 7 days) showed only modest evidence of habituation of cellular activation responses in the PVH and most extrahypothalamic regions Rats bearing retrograde tracer deposits in the PVH and killed 2 hours after acute footshock displayed Fos-positive retrogradely labeled neurons principally in medullary catecholaminergic cell groups, with secondary foci in the hypothalamus, limbic region, and pontine tegmentum This characterization of footshock-responsive systems identifies cell groups that are in a position to (1) mediate acute stress effects on hypothalamic visceromotor neurons, (2) comprise targets for corticosteroid negative feedback effects, and/or (3) underlie habituation of the neuroendocrine limb of the stress response J Comp Neurol 393:244–266, 1998 © 1998 Wiley-Liss, Inc

Localization of Leptin Receptor in the Human Brain

Abstract: Leptin (OB protein), the product of the adipose-specific ob gene, exerts important effects in the regulation of food intake and energy expenditure. Based upon results from animal studies, several groups have suggested that this action may be exerted in the brain, specifically in the hypothalamic region. However, to date, the localization of the OB-R in the human brain has not been described. One aim of this study was to contribute to a better understanding of the role that the central nervous system plays in the pathogenesis of obesity in humans. A first stage was to determine the OB-R expression in the human brain by means of immunohistochemistry and Western blotting. Several brain regions from 17 lean, 14 obese, and 4 diabetic (NIDDM) subjects, obtained from archival autopsy material, were sampled. Brain samples from neocortex, hypothalamus, medualla, limbic system, pineal and cerebellum were routinely processed in paraffin and analyzed with the avidin-biotin immunoperoxidase and diaminobenzidine detection method. Western blotting (WB) analysis was done on fresh brain tissue from an obese patient. Specific OB-R immunoreactivity was localized in the choroid plexus epithelium, ependymal lining, and neurons of the hypothalamic nuclei (arcuate, suprachiasmatic, mamillary, paraventricular, dorsomedial, supraoptic and posterior), nucleus basalis of Meynert, inferior olivary nuclei and cerebellar Purkinje cells. No differences in OB-R immunoreactivity were found among the three groups examined. WB analysis yielded 97- and 125-kD bands in the hypothalamus and cerebellum. In summary, this paper presents the first evidence to indicate the specific localization of the OB-R in the brain of lean, obese and NIDDM subjects.