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[Posterior hypothalamus action on gastric secretion (author's transl)].

Three groups of cats with surgically created total gastric pouches were employed in this experiment. They were divided as follows: in one group the innervation of the pouch was left intact; in another group the symphathetic innervation of the pouch was removed; and in the third group the pouch was completely denervated. It was seen that an infusion of histamine induced gastric secretion in all three groups. And when the secretion became constant it proved to be less acidic and more abundant in the sympathectomized group and also in the group that had suffered complete denervation. It was observed now that stimulating the posterior hypothalamus of the innervated group produced, in all of the cats, a decrease in the amount of acid secreted per unit of time. Consequently, it was seen that a symphathectomy did not eliminate the gastric effects produced when the posterior hypothalamus was stimulated. Specifically, stimulation of the posterior hypothalamus produced an increase in the amount of secretion rather than a decrease. The increase produced in these animals can be shown not to be due to irradiation of the anterior hypothalamus as the same response is obtained when a symphathectomy is combined with a vagotomy. It is, therefore, believed that it may be concluded that the Posterior hypothalamus does not produce its effect exclusively through its nervous pathways. It is believed its effect may possibly be mediated by an unknown substance liberated upon stimulation which then reaches the stomach by way of its blood supply.

Animals↗

Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice.

BACKGROUND: Leptin, a protein secreted from adipocytes, and leptin receptors, expressed in the hypothalamus and fat tissue, regulate energy balance and adiposity. Leptin receptors exist as several forms that are delineated by the length of their cytoplasmic domains. Only the longest form is physiologically active through stimulation of the signal transducers and activators of transcription (STAT) second messenger system. Previous studies demonstrated that chronic ethanol consumption increases body adiposity and circulating leptin levels. This study examined the effect of chronic alcohol intake on the expression of leptin receptors and associated STAT second messengers in the hypothalamus and fat tissue. METHODS: Female C57BL/6 mice were given water or 20% w/v ethanol and Purina 5001 laboratory chow ad libitum for 2 or 5 weeks. Plasma leptin levels were determined by radioimmunoassay and body adiposity was evaluated by measuring the amount of perigonadal fat. Expression of leptin receptors as well as STAT molecules in whole-cell lysates of the hypothalamus and the perigonadal fat were assayed by Western blot analysis. RESULTS: Plasma leptin and perigonadal fat were increased after 5 weeks. The overall expression of leptin receptors was increased while the expression of the physiologically active long form of leptin receptor was decreased in the hypothalamus and the perigonadal fat of ethanol-consuming mice. Ethanol consumption also decreased hypothalamic expression of STAT3, a protein associated with leptin receptor activation in this region of the brain. In contrast, STAT1, a protein associated with leptin receptor activation in adipose tissue, was significantly elevated in the perigonadal fat of ethanol-consuming mice. CONCLUSIONS: Chronic ethanol consumption increases the circulating level of leptin, and this is accompanied by altered expression of leptin-sensing molecules in the hypothalamus and peripheral adipose tissue. These results suggest that chronic ethanol intake affects metabolism by altering the leptin system that regulates energy balance.

Adipose Tissue↗

[The effect of direct stimulation of the dog lateral hypothalamus on transformation of a passive-defensive situational reflex into an alimentary one].

The behavioral effect of electrical stimulation of the lateral hypothalamus with a current of equal parameters in chronic experiments on dogs depended on the signal significance of the surroundings. Stimulation of the lateral hypothalamus against the background of a defensive situational reflex in dogs which were in an experimental situation for the first time, far from evoking orientation to food and the act of feeding, enhanced the background fear reaction. After transformation of the defensive signal significance of the situation into an alimentary one, stimulation of the lateral hypothalamus began to activate the alimentary instrumental reflex and the act of feeding. However, at first the former was manifested irregularly. Combinations of stimulation of the lateral hypothalamus and achievement of the alimentary instrumental reflex with subsequent reinforcement stabilized and enhanced the alimentary instrumental reflex to the stimulation of the lateral hypothalamus.

Animals↗

[The experimental study of the cerebral vasospasm--the micro-circulation on the hypothalamus and the brain stem (author's transl)].

The correlation between the cerebral vasospasm and the micro-circulation in the hypothalamus and brainstem was observed histologically and electronmicroscopically using the colloidal carbon infusion method through the right vertebral artery of dogs. The posterior communicating artery of the dog was ruptured with a fine needle, which resulted in subarachnoid hemorrhage. The colloidall infusion was done at 30 min., 48 hours, 1 week and 4 weeks after the subarachnoid hemorrhage. Results 1) The cerebral vasospasm was confirmed by vertebral angiography on all cases with 30 min., 48 hours, and 1 week after the subarachnoid hemorrhage., In 1 case out of 5 with 4 weeks after subarachnoid hemorrhage vasospasm was also observed. 2) In the period of early spasm, ischemic changes were observed in the anterior-hypothalamus especially in periventricular area of the 3rd ventricle, and supraoptic nucleus. 3) In the period of late spasm, the ischemic changes in the hypothalamus became more conspicous, and these changes propagated into the tectal region of the midbrain and the central gray substance of the aqueduct. 4) In cases of 4 weeks after subarachnoid hemorrhage the ischemic change similar to cases listed in 3) was observed in 1 case whose angiography showed vasospasm. Another 4 cases showed no ischemic lesion at all. 5) Electron microscopic study showed the vasogenic edema in the hypothalamus in the case with cerebral vasospasm. There might be the possibility that vasomoter mechanism in the hypothalamus and brainstem would be involved with the vasogenic edema produced by cerebral vasospasm, which in turn would give a bad influence upon the spasmogenic vessels.

Animals↗

[Orexin A and neuropeptide Y levels in plasma and hypothalamus of rats with chronic renal failure].

OBJECTIVE: To explore the changes of orexin A and neuropeptide (NPY) in plasma and hypothalamus of rats with chronic renal failure (CRF). METHODS: 41 male Wister rats weighing 200 approximately 250 g were randomly divided into three groups: normal group, sham operation group, and CRF group (with the right kidney and 2/3 of the left kidney resected). A certain number of rats were decapitated 4, 8,and 12 weeks after respectively. Their hypothalami were removed and blood collected. Radioimmunoassay was used to measure the levels of orexin A and NPY in hypothalamus and plasma. Automatic biochemical analyzer was used to measure the serum creatinine. RESULTS: The serum creatinine level of CRF rats was both significantly higher than those of the sham operation rats at week 8 and week 12, respectively. The plasma orexin A level of CRF rats at week 12 was 264 pg/ml +/- 62 pg/ml, significantly higher than that of sham operation group (183 pg/ml +/- 56pg/ml, P = 0.039). The hypothalamus orexin A level of CRF rats were 10.5 fmol/mg +/- 2.7 fmol/mg wet weight at week 12, significantly lower than that of sham operation rats (17.4 fmol/mg +/- 3.9 fmol/mg wet weight, P = 0.023). The plasma NPY levels of CRF rats at week 8 and week 12 were significantly higher than those of the sham operation rats (7.1 pmol/ml +/- 1.7 pmol/ml vs 5.0 pmol/ml +/- 0.5 pmol/ml, P = 0.01; and 7.9 pmol/ml +/- 1.1 pmol/ml vs 4.8 pmol/ml +/- 1.1 pmol/ml, P = 0.0008). The hypothalamus NPY level of CRF rats at week 12 were 70 fmol/mg +/- 23 fmol/mg wet weight, significantly lower than that of the sham operation rats (113 fmol/mg +/- 31 fmol/mg wet weight, P = 0.03). CONCLUSION: Loss of renal function may diminish the excretion of orexin A and neuropeptide. The lowering of hypothalamus orexin A and neuropeptide Y levels may be one of the causes inducing anorexia in CRF.

Animals↗

[Effects of male sex hormones on specific uptake and release of 3H-serotonin in the rat hypothalamus in vitro].

With the use of "isotopic method" a study was made of the main parameters of functional activity of serotoninergic elements of hypothalamus--the specific uptake and release of 5-OT. The animals used were sexually mature rats castrated on the first postnatal day. In sexually mature intact males the specific uptake of 3H-5-OT by serotoninergic structures of the anterior hypothalamus was significantly lower than in females. Castration of animals on the first day of life resulted in the increase of specific 5-OT uptake in sexually mature males up to that observed in females. There were no differences between the sexes in the rate of spontaneous release of 5-OT. However, response to K(+)-depolarization in the anterior hypothalamus of intact males was significantly lower than that in females. In the hypothalamus of males castrated neonatally the amplitude of the response to the effect of the depolarizing agent was increase up to the level observed in females. By the results obtained it is indicated that elimination of the effect of male hormones on the first postnatal day results in the increase of 5-OT uptake and release in the hypothalamus of sexually mature rat males.

Androgens↗

Leptin gene expression in the hypothalamus and pituitary of pregnant pigs.

BACKGROUND: Leptin, the 16-kDa peptide hormone product of the ob gene, is a regulatory hormone secreted mainly by adipose tissue. Recent studies have shown leptin production by other tissues, including rat hypothalamus, rat and human pituitary, rat skeletal muscle, kidney and stomach, human and porcine placenta, human mammary epithelial cells as well as endometrial tissues. This hormone is a central modulator of food intake, metabolism and neuroendocrine functions. OBJECTIVES: The aim of the study was to detect and locate porcine leptin gene expression in the different areas of the hypothalamus and pituitary on days 14-16 and 30-32 of pregnancy in pigs. METHOD: Leptin gene expression was analysed by RT-PCR method. PCR products were subjected to sequencing analysis. RESULTS: Leptin mRNA was expressed in the medial basal hypothalamus, preoptic area, stalk median eminence, anterior pituitary, posterior pituitary and adipose tissue on days 14-16 and 30-32 of pregnancy. Sequence analysis of the 258 bp product from the hypothalamus and pituitary confirmed 99% homology with the corresponding region of porcine leptin cDNA sequence. CONCLUSION: Leptin mRNA expression in the porcine hypothalamus and pituitary gland implies its paracrine and/or autocrine role in the regulation of hypothalamic-pituitary axis activity.

Animals↗

[The effect of borneol on level of HA and 5-HT in rat's hypothalamus].

OBJECTIVE: To observe the effect of borneol on level of HA and 5-HT in rat's hypothalamus. METHODS: The levels of HA and 5-HT in rat's hypothalamus were determined before and after p.o. with different amount of borneol by high performance liquid chromatography with electrochemical detection (HPLC-ECD), and the borneol's effect on the levels of HA and 5-HT was also studied. RESULTS: The level of HA in rat's hypothalamus after different dose of borneol were higher than before administration. The level of HA in 20 min group after middle dose increased significantly comparing with before administration (P < 0.01), the others of group after middle dose, the 45 min group after high dose, the 20 and 45 min after low dose were also increased significantly than before administration (P < 0.05). After different dose of borneol, the level of 5-HT in rat's hypothalamus changed as follows: the level of 5-HT after high dose were higher than before administraton (P <0.05 or P < 0.01 ); the level of 5-HT after 5, 20 and 45 min of middle and low dose incrased significantly (P <0.05 or P < 0.01). CONCLUSION: Borneol could increase the levels of HA and 5-HT in rat's hypothalamus.

Animals↗

Effects of tandospirone, a 5-HT1A receptor-related anxiolytic, on the pressor response elicited by stimulation of the posterior hypothalamus in cats.

The effects of tandospirone, a novel 5-HT1A receptor-related anxiolytic, on pressor responses elicited by activation of the posterior hypothalamus were examined in alpha-chloralose-anesthetized cats and compared with those of diazepam and tofisopam. Intravenous administration of tandospirone (0.1-1 mg/kg) and diazepam (1 mg/kg) markedly inhibited the pressor responses to stimulation of the posterior hypothalamus, but did not inhibit the pressor responses to intravenous norepinephrine. The inhibition of the posterior hypothalamus-induced pressor response by tandospirone was significantly antagonized by pindolol (a 5-HT1A receptor antagonist) but not by CGS-8216 (a benzodiazepine receptor antagonist), while the latter reduced the inhibitory effects of diazepam. Tofisopam (a 2,3-benzodiazepine which lacks affinity for benzodiazepine receptors) only attenuated the posterior hypothalamus-induced pressor responses at a high dose (10 mg/kg), which was sufficient to suppress the norepinephrine-induced pressor responses. These results indicate that tandospirone, diazepam and tofisopam all inhibit the pressor response to the posterior hypothalamus activation. In addition, tandospirone and diazepam exert this effect through different mechanisms, the former probably through 5-HT1A receptors and the latter through benzodiazepine receptors.

Animals↗

Exogenous IL-1beta induces its own expression, but not that of IL-6 in the hypothalamus and activates HPA axis and prolactin release.

OBJECTIVE: Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its own production in the hypothalamus as well as that of IL-6. METHOD: Forty five minutes after a single i.p. administration of recombinant rat IL-1beta (5 microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. CONCLUSION: These results indicate that acute peripheral enhancement of IL-1beta may induce neuroendocrine changes also via the immediate activation of its own expression in the hypothalamus, but not that of IL-6 expression in the hypothalamus was found.

Adrenocorticotropic Hormone↗

Activation of the hypothalamus-pituitary-adrenal axis by cytokines.

Activation of the hypothalamus-pituitary-adrenal axis is among the endocrine changes that occur during the acute-phase response to infection or inflammation. These responses have been ascribed to the release of endogenous cytokines. In the present paper a number of studies on effects of interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6) and tumour necrosis factor on the hypothalamus-pituitary-adrenal axis are discussed. In addition some recent data from our laboratory on acute and chronic administration of cytokines are presented. Our data show that continuous infusion of rats with IL-1 elicits a long-term activation of adrenal corticosterone (B) production, suggesting that this peptide is a mediator of the effect of infection or inflammation on the activity of the hypothalamus-pituitary-adrenal axis. Although there is still controversy concerning the site of action of cytokines on the hypothalamus-pituitary-adrenal axis, there is consensus that acutely administered IL-1 increases plasma ACTH and corticosterone levels through activation of hypothalamic CRH neurons. On the other hand, it is possible that during prolonged treatment IL-1 activates the hypothalamus-pituitary-adrenal axis via a rapid effect on hypothalamic CRH neurons and via a delayed effect which results from a direct stimulation of pituitary and/or adrenal cells.

Adrenal Glands↗

[Synthesis of RNA fractions in rat liver during single and multiple stimulation of the hypothalamus].

Specific radioactivity of RNA from rat liver tissue, labelled with 14C-orotic acid and fractionated using thermic phenol method, was altered dissimilarly. In single stimulation of hypothalamus the specific radioactivity of nuclear RNA was increased in RNA-40 degrees fraction than in RNA-55 degrees and RNA-63 degrees ones. A decrease in synthesis of nuclear RNA fractions followed the phase of activation in repeated stimulation of hypothalamus. The distinct increase in specific radioactivity was observed in cytoplasmic RNA (RNA-4 degrees) both in single and repeated stimulation of hypothalamus. The stimulating effect of the prolonged hypothalamus irritation on synthesis of the RNA fractions and on activity of glucose-6-phosphatase and fructose-1,6-diphosphatase disappeared more rapidly than this effect in long-term administration of hydrocortisone. The data obtained suggest that sensitivity of tissue-targets to prolonged hormonal stimulation is distinctly higher than the ability of hypothalamus to activate the synthesis of RNA and enzymatic proteins.

Adrenocorticotropic Hormone↗

[Delta sleep-inducing peptide in the blood and hypothalamus of rats with various resistance to emotional stress].

Enzyme immunoassay was used to study delta-sleep peptide content in blood and hypothalamus in rats of Wistar lines under acute emotional stress. It was found that the content of delta-sleep peptide in blood and hypothalamus of stable rats was higher as compared with rats predisposed to emotional stress. After 1.5-hour emotional stress the content of delta-sleep peptide increased in blood and hypothalamus both in stable rats and predisposed ones. After 3-hour stress there was an increase in delta-sleep peptide content in hypothalamus, and contrary to its decrease in blood in both stable and predisposed animals. It is supposed that delta-sleep peptide along with other oligopeptides is one of the factors determining individual animal resistance to emotional stress, which is supported by significant delta-sleep peptide increase in hypothalamus in stable rats.

Animals↗

Direct somatosensory projections from the spinal cord to the hypothalamus and telencephalon.

Somatosensory input to the hypothalamus has been thought to ascend via an indirect, multisynaptic pathway. However, we have antidromically identified nociceptive spinal cord neurons that project directly to the lateral hypothalamus in rats. Retrograde tracers injected into the lateral hypothalamus labeled many spinal neurons bilaterally within the marginal zone, the lateral reticulated area, the lateral spinal nucleus, and the area surrounding the central canal. An anterograde tracer injected into these areas of the spinal cord labeled fibers and terminals in the lateral hypothalamus and, surprisingly, in a number of telencephalic areas. These findings demonstrate a direct somatosensory projection from the spinal cord to the hypothalamus and several telencephalic regions.

Animals↗

[Intrahypothalamic connections of the lateral hypothalamus].

Using the axon degeneration method by R. Fink and L. Heimer, organization of intrathalamic connections between various areas of the lateral hypothalamus have been studied after unisided electrolitic lesion. At any location of the injury foci, similar patterns are observed in ipsilateral distribution of degenerating fibers along the whole lateral preoptico-hypothalamic area. The most massive degeneration is observed in the zone where the medial forebrain bundle (MFB) fibers run. The degenerating fibers spread forward--into the septal area, and backward--into the mesencephalic part of the brain. The rostral and caudal parts of the lateral hypothalamus, taking part in formation of the MFB collateralies towards the thalamus, are connected with various thalamic nuclei. Massive preterminal degeneration in the perifornical zone and single argerophile granules in the medial hypothalamus convincingly demonstrate an important role of the intermediate zone for connections of its medial and lateral parts with each other. The conclusion that the intrahypothalamic connections of the lateral hypothalamus are realized within the MFB system supports the modern notion on a close connection of the lateral hypothalamus with the system of longitudinal diffuse bundles of fibers of the medial anterocerebral pathway that run through it.

Animals↗

The vasopressor and oxytocic activities of the hypothalamus and neurohypophysis influenced by stimulated alpha-adrenergic transmission during dehydration and subsequent rehydration in the white rat.

Under conditions of equilibrated water metabolism a single dose of methoxamine increased the content of vasopressin in the hypothalamus as well as that of oxytocin both in the hypothalamus and neurohypophysis. During dehydration the depletion of hypothalamic and neurohypophysial vasopressin was more marked in methoxamine-treated animals; this effect, however, was absent in the neurohypophysis on the 2nd day and in the hypothalamus on the 8th day of water deprivation. After two days of dehydration methoxamine inhibited the decrease of oxytocin content in the hypothalamus; simultaneously (2nd and 4th day of dehydration) it intensified this process in the neurohypophysis. During rehydration methoxamine impaired the renewal of vasopressin both in the hypothalamus and neurohypophysis; this effect was most marked on the 8th day of rehydration. On the contrary, it favoured somewhat the renewal of hypothalamic oxytocin in rehydrated rats (such an event was not found on the 8th day of rehydration). Moreover, methoxamine restrained initially (on the 2nd and 4th day of rehydration) the restoration of neurohypophysial oxytocin stores; following eight days of rehydration an opposite effect was here found. It is concluded that the response of the vasopressinergic and oxytocinergic neurons to alpha-adrenergic stimulation, brought about by using methoxamine as pharmacological tool, seems to be depended on the actual state of water metabolism. Impulses from the osmoreceptors may be therefore of some importance in modifying the change in vasopressin and oxytocin synthesis, transport and release resulting from stimulation of alpha-adrenergic transmission through neural chains including units susceptible to methoxamine.

Animals↗

Possible role of hypothalamus and hypophysis in the control of development of pancreas reactivity to the effect of glucose in rat fetuses.

To estimate the role of hypothalamus and hypophysis in the development of functional activity of pancreas, the changes of reactivity of pancreatic B-cells to glucose resulting from encephalectomy and decapitation of fetuses were investigated. Reactivity of pancreas was determined by the changes of insulin secretion induced by the addition of glucose into incubation medium. It was found that, when hypophysis and hypothalamus were removed as a result of decapitation of fetuses from normal or from diabetic pregnant rats on days 17.5-18.5 of development, their pancreas remained insensitive to glucose on 21.5 day. Removal of hypothalamus only when fetuses were encephalectomized on day 17.5 of development also resulted in the loss of sensitivity of fetal pancreas to glucose. Injection of hypothalamus homogenate to encephalectomized fetuses restored the stimulating effect of glucose on B-cells. When pancreas fragments of decapitated fetuses were preincubated together with adenohypophyses of adult rats, the decapitation effect was eliminated, and an increase of glucose concentration in the medium caused an intensive release of insulin. Similar restoring effect was induced by growth hormone (GH) and adrenocorticotrophin (ACTH) when used in in vivo and in vitro experiments. The data obtained give evidence of a possible contribution of hypothalamus and hypophysis to the control of the development of functional activity of pancreas in rat prenatal ontogenesis. However, the mechanism of this regulation remains unclear yet.

Animals↗

[Distribution of horseradish peroxidase-labeled neurons, sources of descending fiber systems, in subcortical brain structures and the hypothalamus of cats].

Location of neurons which initiate different descending fibre systems from amygdaloid nuclei, basal ganglia and hypothalamus to brain stem was studied using the method of horse-radish peroxidase retrograde axonal transport. It was shown that neurons from magnocellular part of the basal amygdaloid nucleus and medial part of central amygdaloid nucleus send their axons to the dorsal hypothalamus, substantia nigra, lateral area of the mesencephalic central grey and midbrain reticular formation at the level of inferior olives. The central amygdaloid nucleus is the main source of projections to the hypothalamus and brain stem structures. It also sends projections to the nucleus of solitary tract and to the dorsal motor nucleus of the vagus. Uncrossed descending fibre systems from the basal ganglia terminate at the pons level, while the uncrossed and crossed fibre systems from dorsolateral and ventromedial areas of hypothalamus descend into the spinal cord. A possible role of the amygdaloid nuclei, basal ganglia, hypothalamus and their different pathways in regulation of somatic and autonomic functions and complex behavioural and emotional responses is discussed.

Amygdala↗