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PubMed2000

[Excitatory amino acid enhance prepro-somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus].

AIM AND METHODS: Contents of glutamate (Glu), asparate (Asp) and expression of prepro-somatostatin mRNA (PPS-mRNA) in rat hypothalamus were measured by using imitated altitude hypoxia rat model, amino acid analyzer and in situ hybridization technique. RESULTS: After rats were subjected to altitude hypoxia, contents of Glu and Asp in hypothalamus and PPS-mRNA expression in periventricular nucleus (PeVN), paraventricular nucleus (PaVN) and arcuate nucleus (ArcN) were increased significantly. Ketamine, a NMDA receptor antagonist, could decrease the number of PPS-mRNA neurons in rat hypothalamus evoked by altitude hypoxia, but had no effect on Glu and Asp contents evoled by altitude hypoxia. CONCLUSION: It is suggested that somatostatin maybe paticipate in altitude hypoxia reaction, Glu can enhance PPS-mRNA expression through NMDA receptor.

Altitude Sickness↗
PubMed2001

Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation.

Glutamate and GABA are two major fast neurotransmitters (excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of excitation/inhibition balance and determine the activity and excitability of neurons in many neuronal circuits. Using neuronal cultures, whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the compensatory regulation of neuronal activity during a prolonged decrease in glutamate excitation. We report here that after a chronic (6-17 d) blockade of ionotropic glutamate receptors, neurons in hypothalamic cultures revealed excitatory electrical and Ca(2+) synaptic activity, which was not elicited in the control cultures that were not subjected to glutamate blockade. This activity was suppressed with acetylcholine (ACh) receptor antagonists and was potentiated by eserine, an inhibitor of acetylcholinesterase, suggesting its cholinergic nature. The upregulation of ACh receptors and the contribution of ACh to the control of the excitation/inhibition balance in cultures after a prolonged decrease in glutamate activity were also demonstrated. Enhanced ACh transmission was also found in chronically blocked cerebellar but not cortical cultures, suggesting the region-specific character of glutamate-ACh interactions in the brain. We believe that in the absence of glutamate excitation in the hypothalamus in vitro, ACh, a neurotransmitter normally exhibiting only weak activity in the hypothalamus, becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. The increase in excitatory ACh transmission during a decrease in glutamate excitation may represent a novel form of neuronal plasticity that regulates activity and excitability of neurons during the glutamate/GABA imbalance.

Acetylcholine↗
PubMed2001

Heavily T2-weighted MR imaging of white matter tracts in the hypothalamus: normal and pathologic demonstrations.

BACKGROUND AND PURPOSE: The MR appearance of white matter tracts in the hypothalamus and the role of the hypothalamus as a memory mechanism have not been sufficiently described in clinical settings. Heavily T2-weighted black-and-white reversed (T2R) images were assessed to reveal their visualization and clinical significance. METHODS: One hundred healthy subjects and three patients with hypothalamic lesions underwent fast spin-echo MR imaging to reveal the postcommissural fornix (PF) and mammillothalamic tract (MT). RESULTS: The PF was identifiable in axial and/or coronal sections in all healthy subjects. No remarkable asymmetry of its size or course was evident. Both anteroposterior and vertical dimensions ranged from 10.5 to 14 mm. The MT was visible in one or two axial sections above the mammillary body in 64% of healthy subjects and in a coronal section in 36%. Two patients with glioblastoma multiforme and lacunar infarct at the hypothalamus presented with anterograde amnesia; T2R imaging revealed involvement of both the PF and MT. The third patient had a suprasellar craniopharyngioma with PF injury sparing the MT resulting from surgical manipulation and was free of memory deficit. Anterograde amnesia was evident only when both the PF and MT were injured. CONCLUSION: T2R images have made a high rate of detection of the PF and MT possible and could provide a more detailed correlation of hypothalamic neuroanatomy and memory mechanism in clinical settings.

Adolescent↗
PubMed2001

Effects of AP-V and bicuculline on somatostatin-positive neurons in hypothalamus of rats subjected to acute hypobaric hypoxia.

AIM: To investigate the effects of 2-amino-5-phosphonovalerate-pharmacology (AP-V) and bicuculline on somatostatin (SST)-positive neurons in hypothalamus of rats subjected to acute hypobaric hypoxia. METHODS: SST-immunoreactivity (IR) and somatostatin mRNA (SS mRNA)-positive neurons were measured by immunohistochemistry and in situ hybridization methods. RESULTS: Compared with control rats, SST-IR and SS mRNA-positive neurons in hypothalamic periventricular nucleus (PeV), paraventricular nucleus (PVN), and arcuate nucleus (ARC) increased after acute hypobaric hypoxia for 6 h (P < 0.01), and these effects were markedly inhibited by AP-V (10 microg, icv), a highly selective N-methyl-D-aspartate (NMDA) receptor antagonist, whereas were strongly enhanced by bicuculline (1.5 mg/kg, ip), a gamma-aminobutyric acid (GABAA) receptor antagonist. CONCLUSION: SST possibly participates in acute hypoxic reaction in hypothalamus, furthermore, glutamate and GABA can affect somatostatin release and synthesis in hypothalamus through NMDA and GABAA receptors respectively.

2-Amino-5-phosphonovalerate↗
PubMed2001

MRI of the hypothalamus and pituitary gland in patients with hyperprolactinaemia following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: Neuroendocrine dysfunction is a known complication of cranial radiation. While growth hormone deficiency is the most common laboratory finding, hyperprolactinaemia is one of the most common symptomatic dysfunction in adult female patients with nasopharyngeal carcinoma (NPC) following radiotherapy. This analysis aims to study the magnetic resonance imaging (MRI) features of the hypothalamus and the pituitary gland in affected patients. METHODS: MRI was performed in 24 patients NPC with hyperprolactinaemia detected 10-52 months following one course of radical radiotherapy. The region of study included the nasopharynx, the hypothalamus and the pituitary gland in 20 patients, while in the remaining four patients, this was limited to the pituitary gland. The estimated radiation dose to the hypothalamus and the pituitary gland was 66 Gy, and six patients also had adjuvant chemotherapy. There was no clinical evidence of tumour recurrence in all 24 patients when hyperprolactinaemia was detected. RESULTS: None of the 24 patients showed any MRI evidence of structural abnormality in the hypothalamic-pituitary region. CONCLUSION: MRI did not reveal any structural abnormality in the hypothalamic-pituitary region of patients who developed hyperprolactinaemia following radiotherapy for NPC.

Adult↗
PubMed2000

[Ketamine and L-NAME inhibit NOS and somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus].

Using altitude hypoxia model, in situ hybridization and NADPH-d histochemistry, we investigated the effects of ketamine and L-NAME (blocker of NOS) on NOS and somatostatin mRNA (SS mRNA) expression in the rat hypothalamus following acute altitude hypoxia. It was revealed that acute altitude hypoxia induced NOS and SS mRNA overexpression in the rat hypothalamus. When pretreated with NMDA receptor antagonist ketamine and L-NAME, NOS and SS mRNA expression were inhibited significantly. These results suggest that NMDA receptor activation participates in the expression of NOS and SS mRNA in the rat hypothalamus subjected to acute altitude hypoxia. Meanwhile, hypothalamic endogenous NO may mediate expression of SS mRNA.

Altitude Sickness↗
PubMedDate not supplied

[Conditioned reflex reproduction of evoked potentials during reinforcement by electrostimulation of the hypothalamus].

Conditioned evoked potentials to stimulation of a limb, a light flash or a short tone were studied on rats in acute experiments with nembutal anaesthesia and in chronic experiments. Electrical stimulation of the hypothalamus was used as reinforcement. Following the pairings of conditioned and hypothalamic stimulation, the appearance of conditioned EP was recorded, as manifest in the period of the previously applied unconditioned signal after its omission. Their emergence was facilitated after high-frequency stimulation of the hypothalamus or administration of galantamine, an anticholinesteraze drug. Coagulation of the hypothalamus did not prevent any manifestation of conditioned evoked potentials.

Animals↗
PubMed1975

H3-phenylalanine incorporation into protein in the pituitary, hypothalamus and cerebral cortex of male rats during postnatal development.

Incorporation of H3-phenylalanine and concentration of protein in the anterior pituitary gland (APG), hypothalamus and cerebral cortex of male rats have been studied during postnatal development from day 21 to 120. APG and hypothalamus showed significantly higher rate of amino acid uptake and protein synthesis during the prepubertal phase, decrease at puberty and an age dependent variation thereafter. Protein concentrations and amino acid incorporation in the APG and hypothalamus are possibly influenced by the higher circulating levels of androgens during sexual maturation in marked contrast to their lack of effect on the cerebral cortex.

Age Factors↗
PubMed1975

Direct fiber connections between the frontal cortex and the hypothalamus in the rat: an electron microscope study.

The direct fiber connections between the frontal cortex and the hypothalamus, especially the ventromedial nucleus and the lateral hypothalamus have been studied by electron microscopy using the orthograde terminal degeneration technique. The results obtained are as follows: Typical electron dense degeneration of the axon terminals is constantly recognized in the neuropil of the lateral hypothalamus on the same side following a lesion of the frontal cortex. On the other hand, the degenerating terminals are found in the field of the neuropil of the frontal cortex following the lesions of either the VMH or the LH, exclusively ipsilaterally. The present study demonstrates the existence of direct fiber connections from the frontal cortex to the LH and from the LH to the frontal cortex in the rat, and suggests the possible existence of a direct projection from the VMH to the frontal cortex.

Animals↗
PubMed1975

Organization of some brainstem and limbic connections of the hypothalamus.

Electrophysiological and anatomical studies allow the formulation of some features of organization of the lateral hypothalamus: (1) The HVM is the major source of modulatory inpur to the lateral hypothalamus; (2) There is a high degree of convergence of afferent paths in the lateral hypothalamus resulting in the same type of postsynaptic firing pattern, whether it be inhibition or excitation; (3) The response to afferent activation is usually quite simple, consisting of either a brief excitatory period or a fifty to several hundred millisecond inhibition. Complex firing patterns in a response to afferent stimulation are rare; (4) Descending hypothalamic output activates two classes of neurons in the midbrain; (a) an output with a strong synaptic drive acting upon cells which are not spontaneously active and which do not respond to arousing stimuli, and (b) an output with moderate to weak synaptic drive acting upon cells that are spontaneously active and excited by peripheral arousing stimuli.

Animals↗
PubMedDate not supplied

[Monoaminergic and aminoacidergic mechanisms of the posterior hypothalamus in realization of the antiaversive effects of anxiosedative and anxioselective agents in various anxiety models].

Experiments using the "illuminated site" and "threatening situation" avoidance tests on rats after preliminary intraperitoneal injection of monoamines, mediator amino acids, and their agonists and antagonists, followed by microinjection of the same combinations into the posterior hypothalamus revealed functional ambiguity in the neurochemical profile of this limbic brain formation in realization of the anxiety states of various genesis. Pharmacological analysis was performed after preliminary injection of various anxiosedative and anxioselective agents into the posterior hypothalamus. It was found that the antiaversive action of chloridiazepoxide, fenibut, and indoter is manifested only under conditions of dominating fear motivation and is mediated by a GABAergic mechanism in the posterior hypothalamus. The anxiolytic effect of campiron is manifested only under negative-stressor zoosocial impact conditions and is mediated by the serotoninergic profile of synaptic switching in this limbic brain formation.

Animals↗
PubMed1976

[The effect of stimulation of the posterior hypothalamus on the electrical activity of the neocortex in chronically premesencephalic cats].

Experiments were carried out on 19 adult cats with chronic brain stem transections at the level of the foremost border of the supperior colliculus. High-frequency electric stimulation of the posterior hypothalamus produced in these cats desynchronization of electrical activity in different parts of the neocortex. A predominant influence from the posterior hypothalamus on the electrical activity of frontal lobes was observed. On the basis of the obtained data, it is suggested that the influences from posterior hypothalamus elicit neocortical activation via thalamic nuclei.

Animals↗
PubMedDate not supplied

[The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus].

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.

Animals↗
PubMed2003

Regulatory domains in the intergenic region of the oxytocin and vasopressin genes that control their hypothalamus-specific expression in vitro.

Previous studies of oxytocin (OT) and vasopressin (VP) cell-specific gene expression in the hypothalamus using transgenic mouse and rat models focused attention on the intergenic region (IGR) as the site of critical enhancer elements. In this study, we used organotypic slice-explant cultures of rat hypothalamus as in vitro models, and particle-mediated gene transfer (biolistics) transfection methods to identify critical DNA sequences in the IGR between the OT and VP genes responsible for hypothalamic-specific gene expression. Reducing the 5' flanking region in the mouse VP gene from 3.5 kbp to 288 bp did not alter the efficacy of its expression in hypothalamic slices. All subsequent VP constructs were based on this 288 bp VP gene construct with changes made only to the IGR. These studies, which used various constructs with OT and VP promoters driving enhanced green fluorescent protein reporter gene expression, demonstrated that the IGR is necessary for OT and VP gene expression in hypothalamic slices in vitro. The DNA sequences in the IGR responsible for both OT and VP gene expression were located in a 178 bp domain immediately downstream of exon 3 of the VP gene. In addition, another domain in the IGR, 430 bp immediately downstream of exon 3 of the OT gene, contained a positive regulatory element for OT gene expression in the hypothalamus. Alignment of the DNA sequences in the 178 and 430 bp domains reveals four common sequences (motifs) that may be candidates for the putative enhancers in the IGR that regulate OT and VP gene hypothalamic-specific expression.

Animals↗
PubMed1992

[Loss of catecholaminergic neuron in the hypothalamus of multiple system atrophy].

Autonomic failure is one of the primary clinical features of multiple system atrophy (MSA); while the hypothalamus is thought to be a higher center regulating the autonomic nervous system. In the hypothalamus, catecholamine depletion had been confirmed by neurochemical studies but no marked changes had yet been demonstrated by pathological studies. Using three MSA and three control cases, we evaluated the quantitative changes of catecholamine (CA)-containing neurons in the hypothalamus. As markers of CA neurons, neuromelanin (NM)- and tyrosin hydroxylase (TH)-containing neurons were stained by Fontana-Masson and the immunohistochemical technique alternatively. Serial coronal sections, 10 microns thick, were evaluated every tenth section for NM neurons, while two sections were evaluated for TH neurons. The distributions of NM and TH neurons were almost identical; most of them were clustered in the periventricular and arcuate nuclei. The mean numbers of NM and TH neurons per slice were significantly lower in MSAs than in the controls (T test, p less than 0.01); the former were 21.0, 31.6, and 13.7 in MSAs and 78.4, 54.1, and 84.3 in the controls, while the latter were 1.5, 15.5, and 20.5 in MSAs and 48.0, 62.0, and 50.5 in the controls. The clinico-pathological correlation was suggested by the significant differences in the number of TH neurons between two MSA cases: a case with severe orthostatic hypotension and a case with a milder one. The ratio of TH and NM neurons, as obtained from the adjusted sections, was constant in all MSA cases, and there was a positive statistical correlation, but it altered in each control case.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Increased lipid peroxidation in the rat hypothalamus after short-term emotional stress].

Concentrations of TBA-reactive substances (TBARS) were measured spectrophotometrically in homogenates of small samples of the brain (hypothalamus, parieto-occipital, sensori-motor and limbic cortex), heart, liver and adrenals of male August and Wistar rats; the former strain is more susceptible to emotional stress than the latter one. Forced isolation of the rats in the restraining plastic cages for 1 h increased the TBARS concentrations in the hypothalamus and liver in August rats only. TBARS accumulation in some tissues correlated with such indices of emotional stress as the changes in relative weight of thymus and adrenals. As regards the brain regions, after 1-hour emotional stress the TBARS levels were no longer different because of an increment in hypothalamic TBARS concentration. However, in control conditions the hypothalamus had significantly lower TBARS levels than any other brain structure both in Wistar and August rats.

Animals↗
PubMed1992

Regulation of gene expression in the hypothalamus: hybridization histochemical studies.

Hybridization histochemistry has bridged molecular biology and neuroanatomy to provide nearly dynamic views of gene expression in the brain--perhaps especially in the hypothalamus. These snapshots of transcript levels with precise anatomical localization have revealed new insights into gene regulation in the hypothalamus under specific conditions. Magnocellular neurons in the paraventricular and supraoptic nuclei produce vasopressin and oxytocin. Transcript levels for these hormones are affected by hyperosmolality, as are those for many other neuropeptides. Patterns of gene expression in the magnocellular neurons in these nuclei during development and under different physiological conditions have been studied less extensively. The parvocellular neurons of the paraventricular nucleus produce corticotropin-releasing factor and thyrotropin-releasing hormone. Expression of the corticotropin-releasing factor gene is regulated by glucocorticoids. Physiological stresses, which activate the hypothalamo-pituitary-adrenal axis, also affect gene expression in the parvocellular paraventricular nucleus. Thyrotropin-releasing hormone is synthesized in a different set of parvocellular neurons in the paraventricular nucleus and in other neurons of the hypothalamus. Expression of the thyrotropin-releasing hormone gene is regulated by thyroid hormone. The suprachiasmatic nucleus contains neurons that produce vasopressin or vasoactive intestinal polypeptide in a circadian rhythm. Future studies using combinations of classical neuroanatomical techniques, hybridization histochemistry and immunohistochemistry will further our understanding of hypothalamic responses to various stimuli.

Animals↗
PubMed2004

[Primary culture of histaminergic neurons in neonatal rat hypothalamus tuberomammillary nucleus].

OBJECTIVE: To establish primary cell culture conditions for tuberomammillary nucleus (TM) histaminergic neurons of neonatal rats. METHODS: The tuberomammillary nucleus was dissected from the posterior part of the hypothalamus of neonatal rats, and neurobasal medium supplemented with B27 was used for the primary cell culture. The cultured neurons were identified by immunocytochemical method (ICC). RESULTS: TM neurons from the hypothalamus of neonatal rats were successfully cultured under the experimental condition and tended to mature morphologically on the days 7 to 9 of culture. The cultured neurons were stained by ICC and the green immunoreaction product was seen in the neurons under the fluorescence microscope, indicating that the cultured neurons were histamine-positive. CONCLUSION: TM neurons in the hypothalamus of neonatal rats can be cultured in vitro, and the primary cultured ones may serve as a cell model in vitro for the researches of central histaminergic system.

Animals↗