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[Effect of melatonin on L-leucine aminopeptidase in the hypothalamus and cerebral cortex of the normal and ovariectomized rat].

The effect of melatonin (500 micrograms/kg weight s.c. for 15 consecutive days) on the L-leucine amino peptidase (LAP) activity of the hypothalamus and brain cortex is studied on castrated and nan castrated rats. There was a significant increase in the LAP activity of hypothalamus (p less than 0.001 v.s. saline group) in the non castrated group, however, no changes were observed in the brain cortex. In the ovariectomized group injected from the 15th to 30th after castration, a very big decrease was recorded in the LAP activity in both the hypothalamus and brain cortex which was not modified by melatonin. This data is studied in relationship to the antigonadotrophic effect of melatonin on the non castrated animals since the changes of this activity in the hypothalamus are inversely related to the gonadotrophin secretion, specially luteinizing hormone.

Animals↗

The cholinergic influences on the oxytocin activity of the hypothalamus and neurohypophysis in long-term dehydrated male rats.

The cholinergic influences on the oxytocin activity of the hypothalamus and neurohypophysis in long-term dehydrated male rats. Acta Physiol. Pol., 1978, 29 (1): 17-25. Rats dehydrated up to 12 days were injected intraperitoneally with carbachol or atropine sulfate in daily doses of 20 microgram/100 g and 1.0 mg/100 g, respectively. In not dehydrated rats atropine increased the oxytocin activity of the hypothalamus and neurohypophysis; carbachol did not influence the oxytocin potency of the hypothalamus but augmented it in the neurohypophysis. During long-term dehydration both carbachol and atropine intensified the depletion of oxytocin in the hypothalamus as well as in the neurohypophysis.

Animals↗

Distribution of luteinizing hormone releasing hormone in the canine hypothalamus: effect of castration and exogenous gonadal steroids.

The effect of exogenous gonadal steroids or orchidectomy on the distribution and concentration of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the dog was studied. Various hypothalamic area of the canine brain were extracted with 90% methanol and processed, and LHRH was assayed, using a specific radioimmunoassay. The highest concentration of immunoreactive LHRH was found in the infundibular, premammillary, preoptic, and suprachiasmatic areas in intact dogs. Measurable amounts of LHRH were found in the mammillary and lateral hypothalamic regions. The hypothalamus in the male dog had significantly (P < 0.05) higher LHRH concentrations 3 mm lateral to the midsagittal line (the lateral hypothalamic area) as compared with the area in the anestrous female dog. Daily estrogen treatment of female dogs with 0.2 mg/day or 1 mg/day, IM, or with testosterone propionate (1 mg/day, IM) for 3 weeks increased LHRH concentration 2.5- to 5-fold in the mammillary, premammillary, and infundibular areas and almost 40-fold in the preoptic, rostral commissural area and in the lateral and dorsal hypothalamic regions. Orchidectomy caused an increase in LHRH concentration in the preoptic and suprachiasmatic area with a concurrent decrease in LHRH in the infundibular area. Therefore, in the dog, LHRH is possibly synthesized or transported (or both) from different regions of the hypothalamus to the median eminence, and the gonadal steroid feedback mechanism is complex, involving multiple sites of action in the hypothalamus and the components of the limbic system.

Animals↗

[Afferent and efferent connections between the hypothalamus and raphe. Study using the technic of retrograde transport of peroxidases].

Projections between rat lateral hypothalamus and dorsal and medial raphe nuclei were studied. Horse radish peroxidase (HRP) was injected into each of these structures and retrogradely labeled neurons were identified. Following HRP injections into lateral hypothalamus (LH) labeled neurons were found into medial and cortical amygdaloid nuclei (AME, ACO), into dorsal thalamic nucleus (MD), in the hippocampal gyrus (HPC) and into medial raphe nucleus (MR). Following HRP injections into medial (MR) and dorsal (DR) raphe nuclei, labeled neurons were found in medial, lateral and posterior hypothalamus. A functional circuit was supposed between midbrain raphe and hypothalamus.

Animals↗

Galanin receptors in human basal forebrain differ from receptors in the hypothalamus: characterization using [125I]galanin (porcine) and [125I]galantide.

Galanin, a 29-amino acid peptide, is uniquely distributed in human basal forebrain and may play a role in cholinergic cell dysfunction in Alzheimer's disease. We report a detailed evaluation of galanin receptors in human basal forebrain (67 +/- 12 years) and hypothalamus (67 +/- 15 years) with radioligand binding techniques. The binding of [125I]galanin (porcine) (agonist) or [125I]galantide [GAL (1-3)-substance P (5-11)-NH2] (putative antagonist) saturated in 2 hr, and only 15% to 30% of either radioligand was removed in the presence of unlabeled peptide. [125I]Galanin or [125I]galantide binding in basal forebrain revealed similar Bmax values, with [125I]galanin having a higher affinity for the galanin receptor. In contrast, [125I]galanin showed a lower affinity and labeled 42% more receptors than [125I]galantide in the hypothalamus. Differences were noted in competition studies of galanin and galanin chimeric peptides (M15, M35, M40 and C7) between [125I]galanin and [125I]galantide binding and in both regions. M35, M40 and C7 showed high affinity for galanin receptors in the hypothalamus with Hill coefficients close to unity, whereas in the basal forebrain these peptides competed differently. 5'-Guanylylimidodiphosphate reduced the specific binding of either radioligand in both regions. Based on the derived data, both radioligands irreversibly bind with high affinity and act as agonists at galanin receptors in human basal forebrain and hypothalamus. Galanin and galanin chimeric peptides compete differently for galanin receptors depending on the radioligand and region tested, suggesting subtype differences.

Adult↗

IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of nitric oxide-mediated signaling.

The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin 2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma) expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. Regulatory functions for IL-2 in the CNS have been suggested. In addition to the spleen, AVP might also mediate some IL-2 effects centrally. In the present study, we evaluated the effect of IL-2 on the in vitro release of AVP from the hypothalamus and amygdala. In addition, we used these release systems to study the possible involvement of NO-mediated signaling in AVP release, based on the reported detection of nitric oxide synthase (NOS) in the hypothalamus and amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and dose-dependent manner. In addition, nitroprusside also induces AVP release. Norepinephrine also induces AVP release from both the hypothalamus, as well as the amygdala. The norepinephrine-induced AVP release is antagonized by phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor-mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma ACTH has already been reported. Our results suggest that in addition to CRF, AVP may also mediate the IL-2 stimulation of ACTH secretion. These data further suggest that in addition to the hypothalamus, the amygdala may also play a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-2 with AVP could clarify the pathophysiologic or toxic effects of high brain levels of IL-2.

Acetylcholine↗

[Effect of scopolamine on the contents of beta-endorphin and oxytocin in hypothalamus, pituitary and plasma in morphine dependent rats].

Male Sprague-Dawley rats weighing 180-220 g were rendered dependent on morphine by repeated injections of morphine in increasing doses for 14 days. 0.3 mg/kg of scopolamine was injected intraperitoneally bid for 3 and 4 days. Control rats were similarly injected with saline. The contents of beta-endorphin (beta-EP) and oxytocin (OT) in hypothalamus, pituitary and plasma were measured by radioimmunoassay. The results showed that both beta-EP and OT in hypothalamus and plasma increased but both were decreased in pituitary in morphine dependent rats (P < 0.01). After scopolamine treatment, the contents of beta-EP increased but OT decreased in hypothalamus (P < 0.01), and both elevated significantly in pituitary (P < 0.01). The results suggested that scopolamine might modulate hypothalamus-pituitary system to affect the release or synthesis of beta-EP and OT in the brain.

Animals↗

[The neurochemical mechanisms of the influence of the posterior hypothalamus on the electrical activity of the forebrain hemispheres and on autonomic reactions in hens].

Effects of i.v. administration of N- and M-cholinergic blocking agents ganglerone and atropine and alpha- and beta-adrenergic blocking agents phentolamine and obsidan (propranolol) on reaction of desynchronisation of EEG and on autonomic reactions (arterial blood pressure, heart and respiratory rates) evoked by low- and high frequency stimulation of the posterior hypothalamus were studied in hens. It was shown that atropine induces a pharmacological dissociation of ascending and descending influences of the hypothalamus by blocking the desynchronizing mechanisms of the upward discharge of the hypothalamus without any apparent changes of autonomic reactions. It was found that the effects of adrenoblocking agents are diametrically opposite to that of atropine in regard to the EEG component, as well as the autonomic components of hypothalamically induced activation reaction. Peculiarities of evolutionary development of neurochemical structures of ascending and descending systems of the hypothalamus are discussed.

Animals↗

Opioids modulate stress-induced proenkephalin gene expression in the hypothalamus of transgenic mice: a model of endogenous opioid gene regulation by exogenous opioids.

Stressful stimuli strongly induce proenkephalin gene expression within the paraventricular nucleus (PVN) of the hypothalamus. A human proenkephalin-beta-galactosidase fusion gene has previously been shown to give correct phenotypic expression and appropriate stress regulation within the hypothalamus of transgenic mice; this model provides high sensitivity, cellular resolution, and ready quantification of levels of proenkephalin gene expression. Here we describe use of this transgenic model to study modulation of stress-regulated gene expression in the PVN by opiates. Acute or subacute morphine administration prior to a hypertonic saline stress produced marked superinduction of transgene expression compared with hypertonic saline stress alone. In contrast, chronic morphine administration decreased basal expression of the transgene, and inhibited stress-induced expression of the transgene. The endogenous proenkephalin mRNA was induced in parallel with the transgene as demonstrated by in situ hybridization; the immediate-early gene c-fos was also regulated in parallel with the transgene. These data suggest that acute or subacute morphine administration sensitizes proenkephalin neurons within the PVN and other regions of the hypothalamus to stress and that chronic morphine administration desensitizes this response. Because the molecular mechanisms regulating the expression of the transgene are well understood, this model provides a useful tool for investigating cellular and molecular effects of opioids on the hypothalamus.

Animals↗

Immunohistochemical localization of nerve growth factor (NGF) and NGF-receptor in the hypothalamus of adult rats.

In the adult mammalian central nervous system (CNS) the nerve growth factor (NGF) has thus far been associated mainly with the metabolic support and pathophysiology of cholinergic basal forebrain (CBF) neurons. Recently, however, the presence of NGF and NGF mRNA has been demonstrated in the hypothalamus of adult mice. In addition there have been reports on the stimulation of the pituitary-adrenocortical axis by NGF. These and other findings suggest the involvement of NGF in hypothalamic functioning. The aim of the present study was to improve immunohistochemical methodologies for the investigation of NGF and NGF-receptor (NGF-r) in the hypothalamus of adult rats. Our results show NGF and NGF-r expression in various regions of the hypothalamus. Moreover, in some areas, distribution and morphology of immunoreactive neurons suggest neuronal colocalization of the two markers. To study the function of NGF in the hypothalamus, anti-NGF antibody was injected in the area of the paraventricular nucleus. We did not, however, find an effect of treatment on NGF-r immunoreactive neurons in this area.

Animals↗

[Changes of Leu-enkephalin in striatum and hypothalamus of rats during hyperbaric oxygen exposure].

The purpose of this study is to investigate the changes of Leu-Enkephalin (L-Enk) content in striatum and hypothalamus of rats during hyperbaric (HBO) oxygen exposure. Thirty-two male rats in the experiment were randomly divided into four groups: normobaric air group, normoxic hyperbaric nitrox group, nonconvulsion HBO group and convulsion HBO group. L-Enk content in striatum and hypothalamus was determined by radioimmunoassay. The results show that L-Enk content in the striatum and hypothalamus of rats exposed to hyperbaric oxygen environment were markedly higher than that of rats exposed to normobaric air and normoxic hyperbaric nitrox. The experimental results suggest that the elevation of L-Enk content in striatum and hypothalamus shows a positive relationship with the HBO exposure duration of animals and that there was no marked relationship with normoxic hyperbaric nitrox environment and compression-decompression method.

Animals↗

Effects of hemodynamic changes on taurine release from posterior hypothalamus of freely moving rats.

AIM: To study the effects of blood volume and vascular resistance on taurine release. METHODS: We used push-pull superfusion technique in the posterior hypothalamus of conscious freely moving rats. Taurine was determined in the superfusate by HPLC with fluorescence detection following automatic precolumn o-phthaldialdehyde (OPA) derivatization. RESULTS: Hypervolemia increased the release of taurine in the hypothalamus. Intravenous infusion of levarterenol (3 micrograms kg-1 min-1) elicited a pronounced pressor response and an increase in the release of taurine. Conversely, a controlled hemorrhagic hypotension or iv infusion of nitroprusside (30 micrograms kg-1 min-1) elicited a hypotension and a decrease in the release of taurine from the posterior hypothalamus. CONCLUSION: In the posterior hypothalamus, taurine might play an important role in central blood pressure regulation.

Animals↗

[Influence of preliminary adaptation to altitude hypoxia on catecholamine concentration in the hypothalamus, adrenals and heart under great physical stress].

Rats were subjected to adaptation to heigth hypoxia in an altitude chamber at the "heigth" 6 km within 7 weeks for 6 hrs a day. Concentration of noradrenaline and adrenaline was normal in hypothalamus; in myocardium content of noradrenaline was also normal but content of adrenaline was slightly decreased; in adrenal glands content of both hormones was distinctly increased. High physical activity (7 hrs swimming) did not alter content of noradrenaline in hypothalamus and adrenal glands of unadaptated rats but decreased 3-fold the content in myocardium. In adaptated rats, by contrast, such loading caused distinct decrease in content of noradrenaline in hypothalamus and adrenal glands and did not affect the content of adrenaline and noradrenaline in myocardium. Thus, adaptation to the heigth hypoxia prevented completely the decrease of catecholamines content in myocardium under loading and simultaneously increased the extent of mobilization of noradrenaline stores in hypothalamus and adrenal glands.

Adaptation, Physiological↗

Immunohistochemical localization of avian pancreatic polypeptide-like immunoreactivity in the rat hypothalamus.

The distribution of avian pancreatic polypeptide-like (APP) immunoreactivity within the rat hypothalamus was investigated with the indirect immunoperoxidase method. APP immunoreactive perikarya are found in largest numbers in the retrochiasmatic area, the arcuate nucleus, and the supracommissural portion of the interstitial nucleus of the stria terminalis. Small clusters of immunoreactive neurons are also consistently observed in the ventral aspect of the medial preoptic area and lateral hypothalamic area, immediately dorsolateral to the optic chiasm and tracts. These neurons are apparent in all animals but are more intensely strained and occur in larger numbers following colchicine pretreatment. Other immunoreactive neurons are visible only in colchine-treated rats and are scattered throughout the anterior and lateral hypothalamic areas and the supramammillary nucleus. Immunoreactive axons and terminal fields present an extensive and highly characteristic distribution throughout the hypothalamus, which in many instances exhibits differential distribution within specific subfields of hypothalamic nuclei and areas. The heaviest concentrations of APP immunoreactive axons are present in the periventricular nucleus throughout the rostrocaudal extent of the hypothalamus, the ventrolateral portion of the suprachiasmatic nucleus, the retrochiasmatic area, the parvocellular paraventricular nucleus, the ventral supraoptic nucleus, the perifornical nucleus, the ventral dorsomedial nucleus, and the arcuate nucleus. Moderate plexuses of immunoreactive fibers are also present in the medial preoptic area, the anterior and lateral hypothalamic areas, the nucleus circularis, the median eminence, and the ventral premammillary area. Other areas, such as the ventromedial nucleus, contain virtually no immunoreactive axons but are encapsulated by a dense plexus of immunoreactive terminals. The distribution of a major component of APP immunoreactive fibers exhibits a marked similarity to that of previously described norepinephrine-containing hypothalamic afferents. Other groups of APP immunoreactive perikarya and fibers appear to represent components of intrinsic diencephalic systems.

Animals↗

Autoradiographic distribution of TRH binding sites in the human hypothalamus.

Using in vitro quantitative autoradiography and [3H]3MeTRH, a selective high affinity radioligand, we examined the rostrocaudal distribution of TRH binding sites in both the infant and the adult human hypothalamus. The saturation curve shows that the [3H]3MeTRH binds with high affinity to a single class of TRH binding sites and is saturable, the apparent constant of dissociation is in the namomolar range. TRH binding sites showed a wide distribution, principally in the anterior and mediobasal levels of the hypothalamus. TRH binding site concentration was highest within the diagonal band of Broca, the lateral preoptic area, the infundibular and the tuberal nuclei. TRH binding site concentration was moderate in the ventromedial nucleus and the medial preoptic area, whereas we observed low densities in the periventricular, paraventricular and mammillary nuclei. The distribution in the infant and the adult is generally similar. However, it is noteworthy that the infant tuberal nuclei displayed a lower binding site density when compared to the adult. On the other hand, the diagonal band of Broca is relatively more labeled in infant. The analysis of the whole hypothalamus allows us to ascertain the absence of lateral asymmetric distribution both in the infant and the adult. No significant difference is noticed when considering as parameters of variation age, sex or post mortem delay.

Adult↗

Brown adipose tissue thermogenesis induced by low level electrical stimulation of hypothalamus in rats.

Brown adipose tissue (BAT) is an energy dissipating form of adipose tissue implicated in non-shivering thermogenesis as well as diet-induced thermogenesis. In the present study, in vivo interscapular BAT (IBAT) temperature was recorded prior to and following low level electrical stimulation (a 30 sec train of 60 Hz, 100 microA 0.5 msec isolated pulses) of various hypothalamic regions in rats. Significant increases in IBAT temperature were observed after stimulation of the anterior, medial preoptic, paraventricular and dorsomedial hypothalamus but not after stimulation of either ventromedial or caudal hypothalamus. For positive sites, IBAT temperature typically increased at 3-4 minutes following stimulation, peaked at 7-8 minutes after stimulation and declined at 20 minutes after stimulation. Although alterations in diet-induced thermogenesis have been reported after ventromedial hypothalamic lesions, the increases in BAT temperature noted in the present study suggest that inhibitory fibers that course through the paraventricular hypothalamus may form part of the central nervous system control of brown adipose tissue thermogenesis induced by overfeeding.

Adipose Tissue, Brown↗

Evidence that the mediobasal hypothalamus is involved in serotonergic stimulation of renin secretion.

The effect of the serotonin-releasing drug parachloroamphetamine (PCA) on plasma renin activity was studied in rats 4 days after surgical lesions of the mediobasal hypothalamus, anterolateral deafferentation of the mediobasal hypothalamus, posterolateral deafferentation, or hypophysectomy. PCA increased plasma renin activity in sham-operated rats, but it failed to increase plasma renin activity in rats with mediobasal hypothalamic lesions or posterolateral deafferentation. The response to PCA was unaffected by anterolateral deafferentation and enhanced by hypophysectomy. There were no significant differences in plasma renin activity in lesioned, deafferented, and hypophysectomized rats injected with saline. The data indicate that the mediobasal hypothalamus is part of the pathway by which central serotonergic neurons affect renin secretion, and that the effect is not mediated via hormones of the pituitary gland.

Amphetamines↗

[LHRH in the human hypothalamus. Immunohistochemical mapping in normal newborn infants or in sudden death infants].

The topographical distribution of neurons containing LHRH has been investigated in newborn hypothalamus using the peroxidase anti-peroxidase technique. In control subjects, LHRH immunoreactive (LHRH-IR) perikarya have been mainly observed essentially in the infundibular nucleus. The preoptic region displayed a moderate density of LHRH-IR cell bodies. High LHRH innervation was observed in the anterior hypothalamus in the lamina terminalis and in the mediobasal hypothalamus in the median eminence, and in the peri- and paraventricular regions. In sudden death infant syndrome, a comparable mapping was observed, except a low density in the mediobasal peri- and paraventricular areas.

Brain Mapping↗