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The functional plasticity of cells of the paraventricular nucleus of surviving sections of the hypothalamus.

Stimulation of the supraoptic nucleus in surviving coronal sections of the hypothalamus elicited in the paraventricular nucleus the appearance of focal potentials reflecting the generation of action potentials of a population of cells. Repeat stimulation was accompanied by a decrease in the descending phase of the focal potentials. Tetanization of the supraoptic nucleus led to the appearance of an additional wave in the descending phase of the focal potentials which was maintained for 15 min. The data obtained attest to the functional plasticity of cells of the paraventricular nucleus of the hypothalamus.

Action Potentials↗

The influence of stimulation of the hypothalamus on the choice of food during maintenance of rats on various salt and water diets.

Electrical stimulation of the lateral hypothalamus of rats maintained on a normal or salty diet with water deprivation leads to an increase in drinking excitability and to a decrease in the thresholds for salty food consumed. The stimulation promotes attenuation of the effects of the "mental" desalting of food that is achieved by a spatial co-placement of the nonsaltiness signal with salty reinforcement, and accelerates the conversion of the signal significance of the conditional stimuli associated with nonsalty and salty reinforcement as well. Electrical stimulation of the hypothalamus accelerates the formation of conditioned reflex aversion to salty food and the inhibition of conditioned reflexes in the direction of the corresponding food dispenser, and intensifies the existing state of thirst as well, imparting to it characteristics of a dominant motivation.

Animals↗

Influence of the posterior hypothalamus on the visual cortex in various states of the reticular formation.

It has been demonstrated in chronic experiments on wakeful rabbits that the stimulation of the posterior hypothalamus by a single electrical stimulus leads to the formation in the visual cortex of a short-latency response which exerts a substantial influence on the formation of the reaction to light stimulation. Depending upon the intervals between the hypothalamic and light stimuli, an initial suppression of the response is observed (1-15 msec), a subsequent selective facilitation of its positive component in the presence of the simultaneous suppression of the negative (20-100 msec), and the complete recovery of the response (200-300 msec). Aminazine and amizil do not alter the directionality of the influence of the stimulation of the posterior hypothalamus on the responses of the visual cortex; however, they do significantly attenuate the degree of expressivity and the dynamics of this influence. Experiments involving local foci in the mesencephalic reticular formation (strychnine, KCl) attest to the inhibitory influence of the latter on the activity of the hypothalamocortical input. The role of the phasic mechanism of hypothalamic control in the realization of the perceptual function of the visual cortex is considered.

Animals↗

A microdialysis investigation of the release of norepinephrine in the hypothalamus induced by 2-deoxyglucose in awake rats.

The level of norepinephrine in the extracellular space of the lateral hypothalamus was measured by means of intracerebral microdialysis in awake rats. The introduction of desipramine (10 mumole) into the perfusing medium did not affect the basal level of norepinephrine, but increased the release of norepinephrine during local K(+)-stimulation. Neuroglycopenia created under the influence of 500 mg/kg of 2-deoxyglucose induced a threefold increase in the level of norepinephrine in the extracellular space of the hypothalamus, which achieved a maximal value in the first 40 min following the introduction of the substance, and thereafter gradually decreased to the basal level.

Animals↗

Role of the lateral and medial hypothalamus in the reproduction of alimentary and defensive instrumental reactions.

It was established in experiments on two dogs that a test electrical stimulation of the lateral hypothalamus reproduces an instrumental movement in the case of a developed alimentary instrumental CR to a tone and does not reproduce it in the case of a developed acid defensive instrumental CR. In the case of an electrical stimulation of the medial hypothalamus, the instrumental movement is essentially not reproduced, either in the alimentary or the defensive situations. The appearance of the instrumental movement with electro-stimulation of the LH in the alimentary situation is associated with activation of the backward conditioned connection from the motivational "alimentary" center of the LH to the representation of this movement in the motor cortex.

Acoustic Stimulation↗

Neuropeptide Y increases the inhibitory effects of clonidine on potassium evoked 3H-noradrenaline but not 3H-5-hydroxytryptamine release from synaptosomes of the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat.

The release of 3H-noradrenaline (3H-NA) and of 3H-5-hydroxytryptamine (3H-5-HT) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat using a superfusion apparatus. Based on concentration-response curves obtained by analyzing the full-time course of the inhibitory effects of clonidine on 3H-NA and on 3H-5-HT release neuropeptide Y (NPY) (1 nM) was shown to significantly increase the ability of clonidine to inhibit 3H-NA release in synaptosomes isolated from the hypothalamus and from the frontoparietal cortex. NPY (1 nM) alone had no effect on K+-evoked 3H-NA release from these regions. In contrast, NPY (1 nM) did not modulate the inhibitory effects of clonidine on 3H-5-HT release in the above mentioned regions. These results indicate that NPY can increase the sensitivity of the alpha 2-autoreceptors belonging to hypothalamic NA and/or to adrenaline nerve terminals and to cortical NA nerve terminals, while the alpha 2-heteroreceptors inhibiting 3H-HT release in the same brain regions appear not to be regulated by high affinity NPY receptors. Thus, alpha 2-autoreceptors and alpha 2-heteroreceptors appear to be differentially controlled by high affinity NPY receptors at least with regard to regulation of 3H-NA and 3H-5-HT release, respectively.

Animals↗

Involvement of adrenergic receptor mechanisms within hypothalamus in the fever induced by amphetamine and thyrotropin-releasing hormone in the rat.

The mechanisms underlying the thermal effects induced by intrahypothalamic administration of either d-amphetamine or thyrotropin-releasing hormone (TRH) has been investigated in conscious rats. Direct administration of d-amphetamine (1-10 micrograms in 1 microliter) or TRH (1-4 micrograms in 1 microliter) into the preoptic anterior hypothalamus caused hyperthermia or fever at the ambient temperature (Ta: 8, 22 and 30 degrees C) studied. The fever induced by d-amphetamine or TRH was due to increased metabolic heat production at Ta 8 degrees C, while at Ta 30 degrees C the fever was due to cutaneous vasoconstriction in the rat. At Ta 22 degrees C, the fever was due to both increased metabolism and cutaneous vasoconstriction. Furthermore, the fever induced by intrahypothalamic administration of TRH was greatly reduced by pretreatment with intrahypothalamic administration of either yohimbine (a blocking agent of alpha-adrenergic receptors), phentolamine (a blocking agent of alpha-adrenergic receptors) or DL-propranolol (a blocking agent of beta-adrenergic receptors) in the rat. However, the fever induced by d-amphetamine was antagonized by pretreatment with yohimbine or phentolamine, but not with DL-propranolol in the rat. These observations indicate that the adrenergic receptor mechanisms within the hypothalamus are involved in the fever induced by both d-amphetamine and TRH.

Animals↗

Separation of pineal extracts by gelfiltration. III. Sheep pineal factors acting either on the hypothalamus, or on the anterior hypophysis of mice and rats in in vitro experiments.

Some compounds, other than melatonin, can be detected in aqueous extracts of sheep pineals, using in vitro bioassays. Mild and simple separation methods are used such as gelfiltration on Sephadex G-25, ultrafiltration through Amicon ultramembranes UM-2and UM-05, followed by gelfiltration on Sephadex G-10 and paper electrophoresis. Some fractions are acting on the hypothalamus, others on the anterior hypophysis of mice and rats. The results are compared with those obtained previously with different extraction and separation methods. Key words: Pineal extract, pineal activities in vitro experiments, hypothalamus, anterior hypophysis, paper electrophoresis.

Animals↗

Development of the human hypothalamus.

The hypothalamus has been claimed to be involved in a great number of physiological functions in development, such as sexual differentiation (gender, sexual orientation) and birth, as well as in various developmental disorders including mental retardation, sudden infant death syndrome (SIDS), Kallman's syndrome and Prader-Willi syndrome. In this review a number of hypothalamic nuclei have therefore been discussed with respect to their development in health and disease. The suprachiasmatic nucleus (SCN) is the clock of the brain and shows circadian and seasonal fluctuations in vasopressin-expressing cell numbers. The SCN also seems to be involved in reproduction, adding interest to the sex differences in shape of the vasopressin-containing SCN subnucleus and in its VIP cell number. In addition, differences in relation to sexual orientation can be seen in this perspective. The vasopressin and VIP neurons of the SCN develop mainly postnatally, but as premature children may have circadian temperature rhythms, a different SCN cell type is probably more mature at birth. The sexually dimorphic nucleus (SDN, intermediate nucleus, INAH-1) is twice as large in young male adults as in young females. At the moment of birth only 20% of the SDN cell number is present. From birth until two to four years of age cell numbers increase equally rapidly in both sexes. After this age cell numbers start to decrease in girls, creating the sex difference. The size of the SDN does not show any relationship to sexual orientation in men. The large neurosecretory cells of the supraoptic (SON) and paraventricular nucleus (PVN) project to the neurohypophysis, where they release vasopressin and oxytocin into the blood circulation. In the fetus these hormones play an active role in the birth process. Fetal oxytocin may initiate or accelerate the course of labor. Fetal vasopressin plays a role in the adaptation to stress--caused by the birth process--by redistribution of the fetal blood flow. Corticotropin-releasing hormone (CRH) neurons of the PVN play a central role in stress response. Thus fetal CRH neurons may play a role in the timing of the moment of birth. Recently, alterations have been described in peptidergic, aminergic and cholinergic transmitters in the hypothalamus in SIDS. Future research will have to establish whether these changes are part of the course of SIDS. A large proportion of the SON and PVN neurons also produce tyrosine hydroxylase (TH). In neonates the majority of TH-immunoreactive neurons colocalizes vasopressin, while in the adult the majority of TH-positive neurons colocalizes oxytocin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Topographic localisation of insulinogenic and insulinoprival areas in the hypothalamus.

Electrical stimulation of hypothalamic areas through stereotaxically implanted electrodes were carried out in conscious male rhesus monkeys. There was a significant increase in immunoreactive insulin (IRI) following laterla hypothalamus (LHA) stimulation. An opposite response was obtained from ventromedial hypothalamus (VMH). Thus, insulinogenic and insulinoprival responses were obtained from feeding and satiety, suggesting a significant role of insulin in the regulation of food intake.

Animals↗

A new type of antiserum to thyrotropin-releasing hormone; detection of new TRH-immunoreactive cell groups in rat hypothalamus.

We produced a new type of antiserum to thyrotropin-releasing hormone (TRH) in rabbits. The immunogen is TRH-BSA, the production of which is based on the formation of an amide bond using carbodiimide (EDC). The specificity of the antiserum was assessed by enzyme immunoassay (EIA) and immunohistochemistry. When using the anti-TRH serum for immunohistochemistry in rat hypothalamus, new magnocellular groups were detected in the ventrolateral parts of the posterior hypothalamus and the dorsal parts of the third ventricle. Colchicine treatment was found not to be necessary to visualize perikarya containing TRH.

Animals↗

H3 autoreceptors and muscarinic acetylcholine receptors modulate histamine release in the anterior hypothalamus of freely moving rats.

To investigate the modulation of histamine release by autoreceptors and heteroreceptors, the rat anterior hypothalamus was superfused through a push-pull cannula with agonists or antagonists of histamine and acetylcholine muscarinic receptors. Superfusion with the H3 receptor agonist (R)-alpha-methylhistamine inhibited, while superfusion with thioperamide (H3 antagonist) enhanced histamine release. Superfusion with carbachol (a mixed M1, M2, M3 agonist) inhibited the release of histamine. The release of endogenous histamine was enhanced on superfusion with atropine (a mixed M1, M2, M3 antagonist). The M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine enhanced the release rate of histamine. It is concluded that in the anterior hypothalamus the release of endogenous histamine is modulated by H3 autoreceptors. Moreover, acetylcholine released from cholinergic neurons also modulates the release of histamine via M1 and/or M3 heteroreceptors.

Animals↗

Presence of interleukin-10 transcripts in human pituitary and hypothalamus.

1. Recent data have shown that interleukin-10 (IL-10) is expressed and acts in mouse pituitary tumor cells and freshly isolated mouse pituitaries. 2. In this study, we show that poly(A+) RNA derived from normal human pituitary and hypothalamus expresses IL-10 message. 3. The majority of transcripts was likely from the pituitary and hypothalamus, and not from lymphocytes in the pituitary and hypothalamic vasculature, since both IL-10 and interferon-gamma mRNA levels, compared to equivalent amounts of RNA from peripheral blood lymphocytes, were much lower. 4. These results indicate that IL-10 may function in human neuroendocrine process as it does in the murine system, thus serving as an important signal molecule for bidirectional communication between the neuroendocrine and the immune systems.

Adolescent↗

Pharmacological model of catecholamine depletion in the hypothalamus of fetal and neonatal rats and its application.

1. The present study aimed to develop a pharmacological model of catecholamine (CA) depletion in the hypothalamus during the period of its morphofunctional development, i.e. in fetal and neonatal rats of both sexes. 2. In the first series of experiments, pregnant females and, hence, fetuses were systemically treated daily from the embryonic day (E) 13 to E20 with the inhibitor of the CA synthesis alpha-methyl-m-tyrosine. The CA concentrations were subsequently measured in the fetal hypothalamus at E21 by high performance liquid chromatography with electrochemical detection (HPLC-ED). In the second series of experiments, neonatal rats were injected with neurotoxin, 6-hydroxydopamine and/or alpha-methyl-m-tyrosine daily from the 2nd postnatal day (P2) to P10. 3. The HPLC-ED assay of hypothalamic catecholamines (CA's) at E21 and P11 showed that both in fetuses and neonates, alpha-methyl-m-tyrosine caused more than 50% depletion of hypothalamic noradrenaline and adrenaline, while the dopamine (DA) level remained unchanged. The combined treatment of neonatal rats with alpha-methyl-m-tyrosine and 6-hydroxydopamine resulted additionally in a 25% decreased level of DA. 4. The influence of CA deficiency on the developing hypothalamic CA system was further evaluated by measuring [3H]DA uptake by nervous tissue in vitro. 5. The CA deficiency caused a 50% drop of [3H]DA uptake by the hypothalamic tissue in treated fetuses suggesting a stimulating effect of CA's on the early development of the CA system. In pharmacologically treated neonatal rats [3H]DA uptake remained at the control level showing no influence of the CA deficiency on the developing CA system after birth. 6. The usefulness of the proposed pharmacological model for studying of CA influence on differentiating hypothalamic target neurons is discussed.

Animals↗

Influence of stimulation of the medial hypothalamus on the interaction of neurons of the rabbit neocortex.

The interaction of neurons of the visual and sensory motor areas of the neocortex of the rabbit before and after stimulation of some medial nuclei of the hypothalamus was investigated by plotting cross- and autocorrelation histograms. Stimulation through bipolar electrodes using bursts of biphasic pulses at a frequency of 100 Hz, current strength 50-200 microA, led to the appearance in freely behaving rabbits of the reaction of avoidance of the place of stimulation. Following stimulation, as compared with resting wakefulness, the number of pairs of neurons functioning in correlation increased to 45%; at the same time, discharges of neurons of the sensory motor area ran ahead of discharges of visual neurons in the pairs up to 120 msec; the periodicity of the coupled discharges was mainly in the theta frequency range. A conclusion regarding the reflection of defense motivation in certain indices of the interaction of the cortical cells in the presence of a tonic conditioned reflex is reached on the basis of a comparison of the interaction of neurons following stimulation of the medial hypothalamus and the midbrain reticular formation, in the intersignal periods during the development of a defense conditioned reflex as well.

Animals↗

Reduced aminergic synthesis in the hypothalamus of the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse.

Diabetes mellitus is commonly associated with reproductive neuroendocrinopathy in both humans and animal models for the disease. Diabetes-associated reproductive failure in the male is a result of multilevel dysfunction within the hypothalamo-pituitary-testicular axis. In view of the known effects of diabetes on hypothalamic gonadotropin-releasing hormone (GnRH) and gonadotropins in chemically-induced animal models for diabetes, we examined hypothalamic aminergic activities (important to the regulation of GnRH release), circulating gonadotropin levels and testicular morphology in the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse. Groups of 2-5 month old (average age: 3.4 months) and 6-11 month old (average age: 8.8 months) diabetic mice were compared with age-matched non-diabetic (C57BL/KsL(-)+/?) male mice. Diabetic mice in both age groups were markedly obese and hyperglycemic. Hypothalamic serotonin synthesis was inhibited in the preoptic area-anterior hypothalamus (POA-AH) in both 2-5 month old and 6-11 month old diabetic mice as well as in the mediobasal hypothalamus-median eminence (MBH-ME) of 6-11 month old diabetic mice. Catecholamine synthesis (norepinephrine and dopamine) was reduced in the POA-AH of 2-5 month old diabetic mice and in the MBH-ME of 6-11 month old mice. These aminergic changes were associated in 2-5 month old diabetic mice with reduced circulating levels of LH and in 6-11 month old diabetic mice, of both LH and FSH. In 6-11 month old diabetic mice, testes were characterized by a thickened tunica albuginea, numerous Sertoli cells and the near absence of any spermatogenic cells. The epididymis from these diabetic mice was devoid of spermatozoa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunocytochemical demonstration of GAP-like immunoreactive neuronal elements in the human hypothalamus and pituitary.

GnRH-associated peptide (GAP)-like immunonreactive elements located in the human hypothalamus were investigated by PAP immunocytochemistry using specific antiserum against [pro-GnRH (14-69) OH]. Immunoreactive neuronal perikarya were distributed in the MPOA, PVN and infundibular nucleus, with the largest numbers of GAP-like immunoreactive perikarya found in the infundibular nucleus. We also detected the coexistence of GAP-like and GnRH-like immunoreactivities in the same neuronal perikarya in the MPOA by using a double immunolabelling procedure. In addition to the above regions immunoreactive neuronal perikarya were present in the region dorsal to the medial mammillary nucleus. GAP-like immunoreactive fibers were distributed in same areas that immunoreactive perikarya were observed. Many immunoreactive terminals were found adjacent to capillaries in the infundibulum. Immunoreactive dots, presumably terminals, were observed in the posterior pituitary and these were particularly evident along the margin adjacent to the anterior pituitary. The distribution pattern and density of GAP-like immunoreactive neuronal elements are compared with those of other mammalian species. We also compared GAP-like immunoreactive elements with that of GnRH as has been previously observed in the human hypothalamus.

Adult↗

Binding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland.

Ghrelin has been proposed as a natural ligand of the GH secretagogue receptor(s) (GHS-R), which was an orphan receptor activated by synthetic peptidyl (hexarelin) and non-peptidyl (MK-0677) GHS to strongly release GH in animals and humans. Herein we studied: 1) the binding of 125I-labeled human ghrelin to membranes from human hypothalamus and pituitary gland; 2) the ability of human ghrelin (either octanoylated or desoctanoylated), as well as of some GHS and neuropeptides to compete with the radioligand. The saturation binding analysis showed, in both tissues, the existence of a single class of high-affinity binding sites with limited binding capacity. The Bmax (maximal number of binding sites) values of ghrelin receptors in the hypothalamus were significantly greater (p<0.001) than those detected in the pituitary, whereas the Kd (dissociation constant) values in the two tissues were similar. 125I-ghrelin bound to hypothalamic membranes was displaced by ghrelin, hexarelin, MK-0677, various GHS antagonists (EP-80317, [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P) and some natural (cortistatin-14) and synthetic (vapreotide) SRIH-14 agonists. In contrast, no competition was seen in the presence of GHRH-44, SRIH-14 or desoctanoylated ghrelin, a ghrelin precursor that is devoid of GH-releasing properties. In conclusion, this preliminary study firstly demonstrates that ghrelin needs octanoylation to bind its hypothalamo-pituitary receptors. These receptors are the specific binding sites for GHS and their antagonists, as well as for SRIH analogs (vapreotide and cortistatin- 14), but not for native SRIH.

Binding, Competitive↗