Showing papers on "Hypothalamus published in 1994"

Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain.

Abstract: POMC, the precursor of ACTH, MSH, and beta-endorphin peptides, is expressed in the pituitary and in two sites in the brain, in the arcuate nucleus of the hypothalamus and the commissural nucleus of the solitary tract of the brain stem. Little is known regarding the functions of melanocortin (ACTH and MSH) peptides in the brain. We report here the detailed neuroanatomical distribution of the MC4-R mRNA in the adult rat brain. The melanocortin 3 receptor (MC3-R), characterized previously, was found to be expressed in arcuate nucleus neurons and in a subset of their presumptive terminal fields but in few regions of the brainstem. The highly conserved MC4-R is much more widely expressed than MC3-R and is pharmacologically distinct. MC4-R mRNA was found in multiple sites in virtually every brain region, including the cortex, thalamus, hypothalamus, brainstem, and spinal cord. Unlike the MC3-R, MC4-R mRNA is found in both parvicellular and magnocellular neurons of the paraventricular nucleus of the hypothalamus...

Mu, Delta, and Kappa Opioid Receptor mRNA Expression in the Rat CNS: An In Situ Hybridization Study

Abstract: The mu, delta, and kappa opioid receptors are the three main types of opioid receptors found in the central nervous system (CNS) and periphery These receptors and the peptides with which they interact are important in a number of physiological functions, including analgesia, respiration, and hormonal regulation This study examines the expression of mu, delta, and kappa receptor mRNAs in the rat brain and spinal cord using in situ hybridization techniques Tissue sections were hybridized with 35S-labeled cRNA probes to the rat mu (744-1,064 b), delta (304-1,287 b), and kappa (1,351-2,124 b) receptors Each mRNA demonstrates a distinct anatomical distribution that corresponds well to known receptor binding distributions Cells expressing mu receptor mRNA are localized in such regions as the olfactory bulb, caudate-putamen, nucleus accumbens, lateral and medial septum, diagonal band of Broca, bed nucleus of the stria terminalis, most thalamic nuclei, hippocampus, amygdala, medial preoptic area, superior and inferior colliculi, central gray, dorsal and median raphe, raphe magnus, locus coeruleus, parabrachial nucleus, pontine and medullary reticular nuclei, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis and cuneatus, dorsal motor nucleus of vagus, spinal cord, and dorsal root ganglia Cellular localization of delta receptor mRNA varied from mu or kappa, with expression in such regions as the olfactory bulb, allo- and neocortex, caudate-putamen, nucleus accumbens, olfactory tubercle, ventromedial hypothalamus, hippocampus, amygdala, red nucleus, pontine nuclei, reticulotegmental nucleus, motor and spinal trigeminal, linear nucleus of the medulla, lateral reticular nucleus, spinal cord, and dorsal root ganglia Cells expressing kappa receptor mRNA demonstrate a third pattern of expression, with cells localized in regions such as the claustrum, endopiriform nucleus, nucleus accumbens, olfactory tubercle, medial preoptic area, bed nucleus of the stria terminalis, amygdala, most hypothalamic nuclei, median eminence, infundibulum, substantia nigra, ventral tegmental area, raphe nuclei, paratrigeminal and spinal trigeminal, nucleus of the solitary tract, spinal cord, and dorsal root ganglia These findings are discussed in relation to the physiological functions associated with the opioid receptors

Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients.

Abstract: The hypothalamo-pituitary-adrenal (HPA) axis is known to be activated in depressed patients. Although direct evidence is lacking, this activation is hypothesized to be due to hyperactivity of corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN). Recent immunocytochemical studies in experimental animals and in humans showed that the number of CRH-expressing neurons correlated with the activity of these neurons. In addition, colocalization of AVP in CRH neurons has been shown to be an index for the secretory activity. Therefore, we estimated the total number of CRH-immunoreactive neurons and their fraction showing colocalization with AVP in the PVN of 10 control subjects and of 6 depressed patients who were diagnosed to be suffering from a major depression or a bipolar disorder. The mean total number of CRH-expressing neurons of the 6 depressed patients was four times higher, and the number of CRH neurons co-expressing AVP was almost three times higher than those in the control group. We also determined the two activity parameters of CRH neurons in the PVN of 2 subjects with a depressive organic mood syndrome or a depressive disorder not otherwise specified. In these two 'non-major depressed' subjects, the activity parameters of CRH neurons were comparable to those of control subjects. Our observations strongly support the hypothesis that CRH neurons in the PVN are hyperactivated in major depressed patients. This hyperactivity might be causally related to at least part of the symptomatology of depression.

A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons.

Abstract: Systemic administration of the cytokine interleukin-1 (IL-1) results in increased secretion of ACTH and corticosterone in rats. The available evidence suggests that the acute effects of IL-1 are exerted ultimately at the level of the hypothalamus to increase corticotropin-releasing factor (CRF) secretion into the hypophyseal portal circulation, and hence the central drive on the pituitary-adrenal system. However, the route(s) and mechanism(s) by which circulating IL-1 gains access to central mechanisms governing pituitary-adrenal output remain poorly understood. In this study, we show that intravenous injection of IL-1 beta provokes time- and dose-dependent increases in the expression of the immediate-early gene c-fos, in identified CRF and oxytocin- producing cells of the paraventricular nucleus of the hypothalamus (PVH). Several cell groups known to be involved in central visceromotor regulation also displayed comparable time- and dose-related activation to systemic IL-1, including the bed nucleus of the stria terminalis, the central nucleus of the amygdala, the lateral parabrachial nucleus, and cell groups of the dorsomedial and ventrolateral medulla. Activation of circumventricular organs, which have been hypothesized to serve as central monitors of circulating IL-1, required doses roughly an order of magnitude above those required to activate CRF neurons in the PVH. Combined immunohistochemical and retrograde tracing experiments revealed many IL-1-responsive cells in the nucleus of the solitary tract and the ventrolateral medulla to be catecholaminergic and to project to the region of the PVH. Discrete and unilateral interruption of ascending catecholaminergic projections from the medulla attenuated IL-1-stimulated increases in Fos immunoreactivity and CRF mRNA in the PVH on the ipsilateral side. Disruption of descending projections from circumventricular structures associated with the lamina terminalis did not affect IL-1-mediated Fos induction in the PVH. We conclude that medullary catecholaminergic projections to the PVH play either a mediating or a permissive role in the IL-1- induced activation of the central limb of the hypothalamo-pituitary- adrenal axis.

Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat.

Abstract: The organization of projections from the four parts of the ventromedial nucleus (VMH) and a ventrolaterally adjacent region tentatively identified as the tuberal nucleus (TU) have been analyzed with small injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Extrinsic and intranuclear projections of each part of the VMH display clear quantitative differences, whereas the overall patterns of outputs are qualitatively similar. Overall, the VMH establishes massive intrahypothalamic terminal fields in other parts of the medial zone, tending to avoid the periventricular and lateral zones. The ventrolateral VMH is more closely related to other parts of the hypothalamus that also express gonadal steroid hormone receptors, including the medial preoptic, tuberal, and ventral premammillary nuclei, whereas other parts of the VMH are more closely related to the anterior hypothalamic and dorsal premammillary nuclei. All parts of the VMH project to the zona incerta (including the A13 region) and parts of the midline thalamus, including the paraventricular and parataenial nuclei and nucleus reuniens. The densest inputs to the septum are to the bed nuclei of the stria terminalis, where the ventrolateral and central VMH innervate the anteroventral and anterodorsal areas and transverse and interfascicular nuclei, whereas the anterior and dorsomedial VMH innervate the latter two. The central, lateral, and medial amygdalar nuclei receive substantial inputs from various parts of the VMH. Other regions of the telencephalon, including the nucleus accumbens and the piriform-amygdaloid, infralimbic, prelimbic, anterior cingulate, agranular insular, piriform, perirhinal, entorhinal, and postpiriform transition areas, also receive sparse inputs. All parts of the VMH send a massive, topographically organized projection to the periaqueductal gray. Other brainstem terminal fields include the superior colliculus, peripeduncular area, locus coeruleus, Barrington's nucleus, parabrachial nucleus, nucleus of the solitary tract, and the mesencephalic, pontine, gigantocellular, paragigantocellular, and parvicellular reticular nuclei. The projections of the TU are similar to, and a subset of, those from the VMH and are thus not nearly as widespread as those from adjacent parts of the lateral hypothalamic area. Because of these similarities, the TU may eventually come to be viewed most appropriately as the lateral component of the VMH itself. The functional implications of the present findings are discussed in view of evidence that the VMH plays a role in the expression of ingestive, affective, and copulatory behaviors.

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Abstract: Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15-17 or Postpartum Days 5-7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V1) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior.

Photoperiodically-induced cycles in the secretion of prolactin in hypothalamo-pituitary disconnected rams: evidence for translation of the melatonin signal in the pituitary gland.

Abstract: Long term changes in the secretion of prolactin were monitored in groups of hypothalamo-pituitary disconnected rams (HPD rams, n = 8) and control rams (HPD sham-operated and unoperated, n = 8) while exposed to an artificial lighting regimen of alternating 16-weekly periods of long days (16L:8D) and short days (8L:16D) for 72 weeks, and during a treatment with subcutaneous constant-release implants of melatonin under long days. The HPD rams showed all the clinical characteristics of complete pituitary disconnection (diabetes insipidus, gonadal regression and slight obesity), and were unresponsive to a range of provocation tests (exposure to a barking sheep dog, cannulation of the jugular vein, injection of serotonin and NMDA) which caused acute changes in the blood plasma concentrations of prolactin in the controls. Nevertheless, there was a clearly defined cycle in the blood concentrations of prolactin in the HPD rams related to the imposed lighting regimen with values 10-fold higher under long days compared to short days (HPD mean +/- SEM: 90.1 +/- 24.7 vs 9.4 +/- 2.0 micrograms/l, long vs short day respectively, P < 0.001). The temporal pattern was very similar to that observed in the controls, although the concentrations of prolactin were higher in the HPD rams and more variable (control mean +/- SEM: 55.6 +/- 3.6 vs 3.0 +/- 0.5 micrograms/l, long vs short day, P < 0.001). There was a corresponding cycle in the growth and moulting of the wool in the HPD rams consistent with a biological response to the photoperiodically-induced changes in the secretion of prolactin. The diurnal rhythm in the blood concentrations of prolactin was absent in the HPD rams, but there was a normal rhythm in the secretion of melatonin. The treatment of the animals with constant-release implants of melatonin under long days caused a marked decrease in the blood concentrations of prolactin in both the HPD and control rams. The overall conclusion is that the endogenously generated daily melatonin signal which encodes daylength acts directly in the pituitary gland to mediate the effects of photo-period on the secretion of prolactin. The photo-period transduction pathway thus by-passes the hypothalamus.

Neuroanatomy and neurotransmitter regulation of defensive behaviors and related emotions in mammals

Abstract: 1. There is suggestive evidence that the septo-hippocampal system and the amygdala are involved in risk assessment behavior, a response to potential threat possibly related to anxiety. In addition, experimental results have been reported implicating the medial hypothalamus in coordinated escape, while the periaqueductal gray matter (PAG) and the median raphe nucleus serotonergic projection to the hippocampus seem to mediate freezing. The latter defensive behaviors are evoked by distal danger stimuli and may be viewed as manifestations of fear. Finally, there is a sound body of evidence indicating that the PAG commands primitive fight or flight reactions elicited by proximal threat, acute pain or asphyxia. These defense reactions may be related to rage and panic, respectively. In contrast, the lateral septal area and the bed nucleus of the stria terminalis have been shown to exert tonic inhibitory influence on defense. 2. Experimental evidence indicates that gamma-aminobutyric acid (GABA) tonically inhibits defensive behavior in the amygdala, hypothalamus and the PAG, an effect opposed by excitatory amino acids. Among monoamines, serotonin (5-HT) has been suggested to facilitate anxiety in the amygdala while inhibiting panic in the PAG. The role of noradrenaline in defense is less clear, although hypotheses implicating the locus coeruleus in anxiety and panic have been suggested. Among peptides, corticotropin-releasing factor (CRF) acting as a central neurotransmitter is thought to mediate behavioral and physiological effects of acute stress, while opioid peptides have been shown to inhibit defense in the amygdala and in the dorsal PAG. Finally, acetylcholine seems to facilitate defensive behavior in the hypothalamus and the PAG. Language: en

Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: potential implications for the syndrome of inappropriate vasopressin secretion

Abstract: We recently demonstrated that sc administered interleukin-6 (IL-6) strongly stimulates the human hypothalamic-pituitary-adrenal (HPA) axis, with mild toxicity and no hypotensive effects. In this study, we evaluated the response of the human HPA axis to escalating iv doses of recombinant IL-6 in six patients with cancer and good performance status who received daily, every 8 h, three equal doses of 0.3-30 micrograms/kg IL-6. The plasma levels of IL-6 assayed by a specific enzyme-linked immunosorbent assay during the 4 h following the first IL-6 injection were elevated for 2-4 h, proportionally to the amount of injected IL-6. Administration of the cytokine was followed by marked elevations of plasma ACTH (53.0-98.6 pmol/L) and cortisol (824.9-1729.9 nmol/L) independently of the IL-6 dose administered, suggesting that the doses employed were at the top of the dose-response curve for these hormones. Interestingly, plasma arginine vasopressin (AVP) levels were also elevated during the 2 h after IL-6 injection in all patients who received a dose of 3 micrograms/kg or more, suggesting that IL-6 activated the magnocellular AVP-secreting neurons and that it might be involved in the syndrome of inappropriate AVP secretion. Cortisol elevations with peaks similar to those observed after the first injection of IL-6 were also detected in plasma sampled every 2 h after the second and third injections, suggesting that there was no rapid tachyphylaxis in response to IL-6 administration. Plasma IL-1 beta and tumor necrosis factor-alpha concentrations, assayed by specific enzyme-linked immunosorbent assays during the 4 h after the first IL-6 injection, were either within the normal range or undetectable, confirming in vitro observations that IL-6 does not stimulate IL-1 beta or tumor necrosis factor-alpha secretion and suggesting that it exerts its effect on the HPA axis and AVP secretion independently of them. We conclude that IL-6 is a potent stimulator of the human HPA axis and a secretagogue of magnocellular AVP secretion, which might be employed as a challenge test of the axis and the magnocellular AVP neuron.

Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion.

Abstract: Chronic salt loading up-regulated the expression of neuronal nitric oxide synthase (NOS) mRNA in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus with a concomitant increase in NOS activity in the posterior pituitary. Once daily ip injection of N-omega-nitroarginine (N-Arg), a NOS inhibitor, significantly inhibited NOS activity in the posterior pituitary in a dose-dependent manner, but did not influence NOS mRNA levels. Two percent salt loading for 3 or 4 days significantly depleted the contents of both arginine vasopressin (AVP) and oxytocin (OT) in the posterior pituitary, and simultaneous treatment with daily injections of N-Arg at a dose of 10 mg/kg significantly enhanced the depletion of both AVP and OT. This effect was dose dependent and paralleled the inhibition of NOS activity in the posterior pituitary. N-Arg treatment had no effect on the levels of both AVP and OT transcripts in PVN or SON. These results suggest that NOS gene expression in the SON and PVN of the rat hypothalamus is increased during hyperosmotic stimulation and suggest a neuromodulatory role for NO in the rat hypothalamo-hypophysial system as an inhibitory regulator of AVP and OT secretion.

Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression.

Abstract: The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA-producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region.

Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration

Abstract: Tumor necrosis factor alpha (TNF-alpha) is a cytokine that is responsible, in part, for several aspects of the acute-phase response to inflammation, including the generation of fever. TNF-alpha has direct effects on central nervous system neurons deep within the hypothalamus that are involved in producing the febrile response, but the blood-brain barrier prevents circulating TNF-alpha from having access to these sites. We therefore have hypothesized that TNF-alpha may be produced in the brain and used as a mediator in the cerebral components of the acute-phase response. We used in situ hybridization to determine the distribution of production of TNF-alpha mRNA in the mouse brain after systemic administration of lipopolysaccharide. During the initial phase of fever, hybridization was observed in perivascular cells and neurons in circumventricular organs, including the vascular organ of the lamina terminalis, median eminence, and area postrema, as well as along the ventral surface of the medulla; hybridization was also prominent over many cell in the meninges. During the late phase of the response, hybridization was observed over neurons in the pericircumventricular nuclei such as the anteroventral periventricular and arcuate nuclei of the hypothalamus and the nucleus of the solitary tract. TNF-alpha produced by a cascade of neurons within the brain may participate in the complex autonomic, neuroendocrine, metabolic, and behavioral responses to infection and inflammation.

Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain.

Abstract: The conversion of androgens to estrogens by aromatase cytochrome P450 (P450AROM) is an important step in the mechanism of androgen action in the brain. In adult rats, P450AROM activity (AA) is regulated by androgens in the preoptic area and medial basal hypothalamus, but is constitutive in the amygdala. This study was undertaken to determine the distribution of P450AROM messenger RNA (mRNA) and AA in adult rat brain and examine the effects of steroid treatments on their concentrations in various brain regions. AA was determined by a sensitive assay that measures the production of 3H2O during the conversion of [1 beta-3H]androstenedione to estrone. P450AROM mRNA was measured by a ribonuclease protection assay using a RNA probe complementary to the 5'-coding region of rat P450AROM mRNA. The 32P-labeled P450AROM probe protected two mRNA fragments in brain tissues that expressed AA (preoptic area, medial basal hypothalamus, amygdala, and hippocampus). The larger protected RNA fragment was 430 nucleotides (nt)...