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[Morphologic and biochemical changes in the hypothalamus in hormonally stimulated sheep].

The effect of exogenous hormonal preparations (PMSG, SG, PMSG + PGF2 alpha and FSH) was studied as exerted on neurosecretion and on changes in the nuclear volume of nucleus paraventricularis, nucleus ventromedialis, nucleus infundibularis and nucleus tuberomamillaris, and on histological changes in the third cerebral ventricle. Changes in catecholamine concentrations were determined in the rostral, medial, and caudal hypothalamus of the ewes. The study was performed with 28 ewes of the Slovak Merino breed during the oestrus period. The oestrus was synchronized by the Agelín vaginal tampons (Spofa). The ewes of four experimental groups were stimulated by the administration of 1000 I.U. PMSG (Antex-Leo), 1000 I. U. Serum Gonadotropin (Bioveta Ivanovice na Hané), 1000 I. U. PMSG with 250 micrograms Oestrophan inj. (Léciva Praha), and 450 I. U. Folistiman (VEB Arzneimittelwerk Dresden, GDR). The brain samples were processed by common histological methods. A caryometric analysis was performed at 3000-fold magnification and by measurement of 200 cells of one sample. The data were subjected to mathematical processing after Fischer and Inke (1956). The amount of neurosecretory material was evaluated by light microscopy (Nakahara, 1963). The multiplication of neurosecretion in the hypothalamic nuclei testifies to the fact that the administration of hormonal preparations stimulates the function of hypothalamic structures, which corresponds with the results of the caryometric analysis. It also ensues from the results that the administration of serum gonadotropins (PMSG and SG) at the dose of 1000 I. U. results in a statistically significant decline (P less than 0.001) of the concentrations of norepinephrine in the rostral, medial and caudal hypothalami of the ewes, although the PMSG preparation has a more pronounced effect when compared with SG. The hormonal stimulation with PGF2 alpha and with FSH causes no significant changes in the concentration of norepinephrine in the hypothalamus of the ewes. As norepinephrine is considered as a neurosecretion inhibitor, the multiplication of neurosecretion in the hypothalamus nuclei after stimulation with serum gonadotropins correlates with the decline of hypothalamic norepinephrine concentrations.

Animals↗

[Changes in the substance P content of the blood and hypothalamus during experimental emotional stress].

A study was made of the content of substance P in the blood and hypothalamus of Wistar rat brain in acute and chronic emotional stress and after intraperitoneal injection of substance P in a dose of 250 mg/kg. A possibility was demonstrated of inducing long-term changes in the content of substance P in the hypothalamus after a single injection. Exposure to a single 24-hour stress was followed by an increase in the substance P content in the hypothalamus.

Animals↗

Anatomical and functional effects of estrogen-induced prolactinomas on the rat hypothalamus.

Although estrogen-induced prolactinomas have been widely studied, little attention has been accorded to local pressure effects of the tumor on the hypothalamus and portal vasculature. To portray the magnitude of this phenomenon, four groups of 12-13-week-old female Fisher 344 rats were studied. Group 1 was an intact control receiving a subcutaneously (SC) placed placebo pellet; group 2 was an ovariectomized control with a SC placed placebo pellet; group 3 was ovariectomized with a 10 mg SC placed diethylstilbestrol (DES) pellet; and group 4 was ovariectomized receiving both 10 mg DES and 10 mg SC placed bromocriptine pellets. Blood samples were obtained at 4 weeks, and the animals were sacrificed at 8 weeks after pellet implantation at which time blood, pituitary and hypothalami were obtained. At 4 weeks serum prolactin levels were similarly and significantly elevated above the control groups in both the DES and DES/bromocriptine groups. By 8 weeks, however, serum prolactin level(s) in the DES-treated animals had tripled from the 4-week value, while levels in the DES/bromocriptine-treated animals were unchanged from the 4-week values. This finding matched the observation that the DES-treated animals had pituitaries 2.5-fold heavier than the DES/bromocriptine animals. The gross and histologic structure of the hypothalami and portal vessels were markedly disrupted in DES-treated rats and much less so in the DES/bromocriptine-treated group. These findings lead us to speculate that the pathogenesis of DES-induced prolactinomas proceeds in two phases: First, there is an early chemical induction phase in which estrogen directly and indirectly stimulates lactotrope proliferation and, second, a mechanical disinhibition phase, where tumor-induced destruction of the hypothalamus and portal vessels unleashes the pituitary from the dopaminergic restraining effects of the hypothalamus.

Animals↗

[The hypothalamus in neurosurgical patients (pathologo-anatomic and clinico-electroencephalographic correlations)].

Only a third of the cases who have neurosurgical abnormality has been found to develop irreversible hypothalamus affections caused by tumor growth, hemorrhages, and ischemic infarcts. Microcirculatory abnormalities made up three typical morphological variants, viz. venous congestion, impaired rheological and coagulative properties of blood, and anemia in the vasculature predominantly occur in the other cases. Acute bilateral destruction in the medial segments of the hypothalamus corresponds to its profound functional inhibition. As its morphological substrate, sharp irritation of the hypothalamus (the diencephalic and catabolic syndrome has widespread rheological and coagulative abnormalities in its structures associated with largely reversible dystrophic changes in nerve cells.

Adult↗

[Response of the secretory glands of the stomach to peptide injection into the hypothalamus, caudate nucleus and amygdala].

In chronic experiments on dogs, microapplication of neurotensin into the hypothalamus or amygdala combined with histamin or pentagastrin stimulation of the stomach secretory function significantly reduced the stomach secretion. Microapplication of somatostatin into the hypothalamus or amygdala combined with i.v. administration of pentagastrin increased two-fold the stomach secretion. The same increasing effect occurred after microapplication of methionin or leucin-5-enkephalin retroanalogue into the hypothalamus or amygdala.

Amygdala↗

Steroid regulation of somatostatin mRNA in the rat hypothalamus.

The participation of gonadal steroid hormones in the regulation of the expression of the somatostatin gene in the hypothalamus and cerebral cortex was studied by using a quantitative densitometric hybridization assay which allows the direct measurement of specific somatostatin mRNA levels. The levels of somatostatin mRNA in hypothalamus were found to be significantly decreased following gonadectomy in both male and female rats (67% in males and 75% in females). Moreover, with in situ hybridization histochemistry somatostatin mRNA was similarly reduced following gonadectomy in the dorsal portion of the periventricular region and in the ventromedial nucleus. Estradiol dibenzoate treatment reversed the decrease in somatostatin mRNA in females within 24 h and testosterone treatment reversed the decrease in castrated males. In contrast, there was no significant change in cerebral cortex somatostatin mRNA levels after gonadectomy. These results suggest that sex steroids are involved in the regulation of the somatostatin gene in the hypothalamus, possibly at the transcriptional level.

Animals↗

[Effects of repeated acupuncture action on pain sensitivity and beta-endorphin contents of the hypothalamus and midbrain of the rat].

Changes in latencies (L) of nociceptive (NC) reactions of hot plate (HP) tail flick (TF) tests and dynamics of beta-endorphin (beta-ED) in hypothalamus and midbrain were studied in albino rats receiving 15 sessions of acupuncture (A) (20 min daily in bilateral Ho-Ku). It was shown that repeated A facilitated prolongation of LHP and LTF as compared to baseline and control levels. A decrease of the anti-NC systems capacity for activation in response to each A stimulation was observed. The dynamics of beta-endorphin in hypothalamus showed an opposite tendency as compared to that in midbrain. It is suggested that such a correlation of beta-ED activities in midbrain and hypothalamus might be one of the reasons for anti-NC mechanisms adaptation to A.

Acupuncture Therapy↗

The responsiveness of alpha 2-adrenergic receptors in hypothalamus of vasopressin-hypertensive rats.

Administration of clonidine produced biphasic changes in the type II inhibitor activity (endogenous inhibitor of protein kinases which specifically regulates phosphorylation mediated by cGMP-dependent system). Small doses of clonidine (10-50 micrograms/kg) produced an increase while large doses (200-1000 micrograms/kg) induced a decrease in the type II inhibitor activity. The both actions of clonidine were greatly reduced in vasopressin hypertensive rats suggesting subsensitivity of alpha 2-adrenergic receptors. Subsensitivity of postsynaptic alpha 2-receptors was also observed in anterior hypothalamus in in vitro experiments. Incubation of anterior and posterior hypothalamic slices with clonidine resulted in concentration-dependent increase in cGMP content and a decrease in the type II inhibitor activity. The clonidine action in anterior hypothalamus of vasopressin-hypertensive rats was greatly reduced. In contrast, the clonidine action in posterior hypothalamus was the same in vasopressin-hypertensive as in the control rats.

Animals↗

Alzheimer's disease and the pivotal role of the hypothalamus and the intrinsic opioid system.

Although the "cholinergic hypothesis" of the pathophysiology of Alzheimer's disease has received great attention during the past years, it has recently come under increasing criticism specifically owing to failure of therapeutic endeavors based on this premise. As the potential broad role of the intrinsic opioids in the neurochemical modulation of diverse brain functions emerges, the realization that these data may be reconciled to a unifying hypothesis underlying the nature of some chronic dementing diseases (including Alzheimer's disease, Korsakoff disease and Parkinson's disease) occurs. Certain specific characteristics of the known pathologic changes and neurotransmitter deficits of Alzheimer's disease may be explained based on an early vulnerability of the hypothalamus combined with derangements of endorphinergic functions which follow. The latter may be implicated in the subsequent degeneration of structures receiving projections from the arcuate nucleus of the hypothalamus. This is based on the known role of endorphins in the modulation of central neurotransmitters and specifically acetylcholine activity. In addition, the reciprocal neuroendocrine and neuroimmunologic interactions mediated through the hypothalamus, may be of further importance in the evolution of Alzheimer's disease.

Alcohol Amnestic Disorder↗

Maturation of 17 beta-estradiol binding protein in the hypothalamus and anterior pituitary of male rats.

Levels of estrogen binding proteins in the cytosol of hypothalamic and pituitary tissue of male rats at different ages were estimated. Two classes of estrogen binding sites were detected in 13 and 20 days old animals. The number of high affinity estrogen binding sites (K = ca. 2 x 10(-10) mol) of the hypothalamus was slightly larger in 13 days old animals, then decreased to constant levels at the age of 20 days and no changes were observed thereafter. Levels of low affinity binding sites of the hypothalamus (K = ca. 5 x 10(-9) mol) decreased with age and were no longer detectable in 30 days old animals. Similarly, a decrease of low affinity estrogen binding sites with age was recorded for pituitary cytosol samples and this class of receptor sites was no longer observable in 30 days old male rat. At 13 days high levels of high affinity 17 beta-estradiol binding protein was registered and minimal numbers of binding sites were found at 20, 30 and 40 days. Thereafter, the levels remained constant until 100 days and were similar to values observed in the 13 days old male animals. Apparent affinity constants of two classes of binding sites in hypothalamus and pituitary were similar...

Aging↗

[Dependence of changes in the luliberin level in the synaptosomal fraction of the olfactory bulbs and various areas of the hypothalamus on the level of sexual activity in male rats].

The paper is devoted to a study of the level of LH-RH in the synaptosomal fraction of the olfactory bulbs, preoptic area and mediobasal hypothalamus, and the blood level of HL in adult male rats with sexual activity after noradrenergic denervation of the preoptic area using 6-hydroxydopamine. A neurotoxic effect of 0.1% solution of ascorbic acid, preventing 6-hydroxydopamine disintegration, was noted. Both sexual activity and the level of LH-RH in synaptosomes of the preoptic area were lowered in male rats with noradrenergic denervation of the preoptic area. The maximum blood level of LH was observed during exposure to a recipient female rat. LH-RH concentration in the synaptosomal fraction of the olfactory bulbs being raised, that in the mediobasal hypothalamus lowered. The results were indicative of the involvement of HL-RH-synthesizing cerebral neurons with terminals in the olfactory bulbs, preoptic area and mediobasal hypothalamus in the regulation of sexual behavior, and the interaction of LH-RH-containing terminals with noradrenergic nerve endings at the level of the preoptic area.

Animals↗

[The role of the perifornix area of the hypothalamus in forming alcoholic motivation in rats].

In rats with alcohol motivation on the model of water deprivation with substitution of water for 20% ethanol solution, motivatiogenic "drinking centres" of the hypothalamus initiate in response to electro- and chemostimulation (acetylcholine) behavioural reactions of search and taking of alcohol and not of water. Electrolytic ablation of "thirst centres" of the perifornical hypothalamus area in rats with a formed attraction to alcohol is accompanied by a decrease of its taking during 3-5 days of observation. Microinjections of dipsogenic peptide angiotensin II, unlike acetylcholine administration, do not initiate taking of water or alcohol, but elicit only appearance of orienting-investigating, alimentary, sexual and other behavioural reactions. It is suggested that formation of alcohol motivation in these conditions is connected with a change of neurophysiological and neurochemical properties of the hypothalamus "thirst centres" initiating an active search and taking of alcohol and not of the water in rats with experimental alcoholism.

Acetylcholine↗

Chronic treatment with desmethylimipramine increases the oxytocin content in the hypothalamus and neurohypophysis of normal and pinealectomized male rats.

The effect of chronic treatment with desmethylimipramine (i.p., 10 mg/kg; twice daily over 5 days) on the content of oxytocin in the hypothalamus and neurohypophysis of normal and pinealectomized male rats has been investigated. Pinealectomy resulted in a decrease of oxytocin content in the hypothalamus and neurohypophysis. Treatment with desmethylimipramine (desipramine; DMI) was followed by a distinct increase of the oxytocin potency in the hypothalamus and neurohypophysis in both normal and pinealectomized rats. It may be supposed that chronic treatment with DMI inhibits the oxytocin release from neurohypophysis.

Animals↗

[Temperature sensitivity of the hypothalamus as affected by an increase in the heat content of the body].

To obtain a vascular thermoregulatory response of the ear floor, the hypothalamus had to be heated by 0.59 +/- 0.03 degrees C. After preliminary intraperitoneal administration of subthreshold amount of heat (195.7 +/- 8.9 cal.) constituting 50.7 +/- 1.8% of the threshold (386.4 +/- 14.3 cal.) the hypothalamus had to be heated by 0.19 +/- 0.01 degree C only to obtain the same response in the animal. The change of own temperature sensitivity of the hypothalamus in increased heat contents of the organism might be an auxiliary mechanism for estimation of the heat contents changes by the organism.

Acclimatization↗

[LH-RH content in different parts of the hypothalamus and blood of rats with an altered level of thyroid hormones].

Luliberin (LH-RH) in the preioptic region of the hypothalamus, the region of the arcuate nuclei, and of the medial eminence, the region of the dorsomedial nuclei and in the blood serum was studied in intact female rats with a stable 4-day cycle, and also in thyroidectomized female animals. LH-RH content rose significantly during the morning hours of the proestrus both in the cyclic and in the tonic centres of the hypothalamus. At the same time there was an increase of this hormone secretion. Thyroidectomy blocked the LH-RH synthesis and secretion elevation in both areas at the proestrus stage. In the region of the dorsomedial nuclei LH-RH content remained at the same level in the both groups of the animals. During the day at the proestrus stage, intact animals displayed definite regularities in the LH-RH synthesis in both the hypothalamic centres, and also in its secretion (absent in thyroidectomized animals). The data obtained indicated disturbance of cyclic discharge of LH-RH after thyroidectomy to be largely connected with reduciton of the hormone level in the cyclic centre localized in the preoptic region of the hypothalamus.

Animals↗

[Comparative study of sympathetic and parasympathetic discharges in the autonomic nerves during stimulation of different structures of the cat hypothalamus].

Simultaneous recordings of hypothalamo-parasympathetic and hypothalamo-sympathetic evoked discharges in anesthetized cats demonstrated that both parasympathetic discharges in the pelvic nerve and sympathetic discharges in the splanchnic nerve of the lowest threshold and shortest latency could be obtained from stimulation of the posterior hypothalamus. The focus of the maximal neuronal activated elicited by stimulation of afferent fibres of visceral nerves and the focus evoking maximal efferent reactions of parasympathetic and sympathetic nerves were located in the same region of the postero-lateral hypothalamus. It is supposed (as a working hypothesis) that convergent polysensory neurons of the hypothalamus are also polyeffector divergent elements of the hypothalamo-visceral reflex system.

Action Potentials↗

Effects of gonadectomy and sex hormones on the levels of noradrenaline and dopamine in rat hypothalamus.

The levels of noradrenaline and dopamine were determined in the homogenates of the hypothalamus of rats of either sex. The determinations were done in intact rats, after sham gonadectomy, 6 and 9 weeks after gonadectomy, and in gonadectomized rats receiving 6 weeks after gonadectomy one dose of oestradiol cypionate (females) or testosterone cypionate (males). Catecholamines were determined fluorimetrically. The changes of the determined catecholamines differed in the hypothalamic homogenates in males and females after gonadectomy. Following orchidectomy the noradrenaline level rose, while after ovariectomy the level of this catecholamine decreased. Contrary to this, in ovariectomized rats the dopamine level was significantly raised after the operation. This change was reversible as observed after administration of oestradiol cypionate. Orchidectomy and testosterone cypionate injection had no effect on the dopamine level in the hypothalamus. The role of these catecholamines in the processes connected with the regulation of the hypothalamus-hypophysis-gonad axis is discussed.

Animals↗

[Impregno-architectonic study of the medial part of the hypothalamus in sheep].

Impregno-architectonics of neurons in the nuclei of the medial part of hypothalamus was studied in two-month and adult female and male sheep using the methods after Ramón-Moliner and Golgi-Cox. Types of neurons in the hypothalamic nuclei are given, morphology of synaptic conjugations and orientation of nerve processes are described. Ventromedial nucleus has the most interesting structure as a part of the medial hypothalamus: it is ring-shaped in cross-section with paucicellular center, contains various types of neurons and all kinds of synapses which can occur in hypothalamus. Only small numbers of neurons in the pars caudalis of tuberomammillary nucleus, similarly like in nucl. supraopticus and nucl. paraventricularis, are impregnated so that they can be supposed to belong to true neurosecretory nuclei.

Animals↗