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Prehepatic portal hypertension in rats modifies norepinephrine metabolism in hypothalamus, medulla oblongata and portal vein.

The present experiments investigated the possible relationship between portal hypertension and norepinephrine metabolism in the central nervous system (hypothalamus and medulla oblongata) and the portal vein in the rat. Group I (72), portal hypertensive, and group II (70) sham-operated animals, were sacrificed day 14, and endogenous norepinephrine content, uptake and release from hypothalamus, medulla oblongata, and portal vein were investigated. In group I our results showed increases in norepinephrine storage (69%; 8.3%) and release (19.7%; 43.8%) and a diminished uptake (42.3%; 27.5%) in the hypothalamus and medulla oblongata, respectively. Portal veins showed a decreased content and uptake (62.5% and 43.5%, respectively) and increased release (25%) compared to group II rats. These results suggest a close relationship between the central nervous system and rat portal hypertension, perhaps related to modifications of central sympathetic activity.

Animals↗

Ultrastructural organization of regenerated serotonin axons in the dorsomedial hypothalamus of the adult rat.

The ultrastructural organization of regenerated serotonin (5-HT) axons was examined in the dorsomedial hypothalamus (DMH) of the adult rat using high-resolution radioautography after intraventricular infusion of [3H]5-HT. An analysis of the microenvironment of the [3H]5-HT-labelled terminals in the DMH was made 30 and 50 days after unilateral injection of 5,7-dihydroxytryptamine (5,7-DHT) or vehicle solution into the dorsolateral hypothalamus. In sham-treated animals [3H]5-HT-labelled axons were small, contained many small clear vesicles, one or more large granular vesicles, and showed only rare synaptic specializations. In 5,7-DHT-treated animals the internal organization of [3H]5-HT-labelled profiles resembled that of sham-treated animals. A tendency toward increased synaptic frequency was found for [3H]5-HT-labelled terminals in the 5,7-DHT-treated group 50 days post-lesion, and an increase in the number of [3H]5-HT-labelled terminals abutting unlabelled perikarya was found in both 30- and 50-day post-lesion groups as compared to sham-treated groups. No other differences in ultrastructural environment were found between sham- and 5,7-DHT-treated animals at either 30 or 50 days post-lesion. These results suggest that 5-HT fibres in the hypothalamus regenerate with a great deal of cellular specificity.

5,7-Dihydroxytryptamine↗

Involvement of both opiate and catecholaminergic receptors of ventromedial hypothalamus in the locomotor stimulant action of thyrotropin-releasing hormone.

To explore the mode of the locomotor stimulant action of thyrotropin-releasing hormone (TRH), rats with or without administration of opiate or catecholaminergic receptor antagonists were infused with TRH through previously implanted hypothalamic cannula. Administration of TRH, but not the normal saline or TSH, into the ventromedial hypothalamus caused an enhancement in both the gross movements (including stimulation of forward locomotion, head and body rearing) and fine movements (including increased grooming and head swaying). The locomotor stimulant action provoked by TRH was antagonized by pretreatment of ventromedial hypothalamus with either an alpha-adrenergic receptor antagonist (yohimbine), a dopaminergic receptor antagonist (haloperidol) or an opiate receptor antagonist (naloxone), but not with a beta-adrenergic receptor antagonist (propranolol). The results indicate that all the adrenergic, dopaminergic and opiate receptors in the ventromedial hypothalamus are involved in the TRH-induced hyperactivity in the rat.

Animals↗

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus.

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin greater than imipramine greater than desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a "suicide" inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verfied that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.

Amitriptyline↗

Features of the coordinated activity functionally identified neurons in the hypothalamus in different motivational-emotional states.

Coordinated activity of hypothalamic neurons associated with motivational and reinforcing systems were studied in functional states arising from hunger, satiation following food deprivation, "victim" cries, and electrical stimulation of the emotionally positive (lateral hypothalamus, lateral preoptic region) and negative (dorsomedial tegmentum) reinforcing structures of the hypothalamus. Activity characteristics were reflected in the magnitude, sign, and dynamics of correlations, and depended on the ratio of motivational and emotional components of behavior. The reciprocal nature of the statistical significance of the activity of these neurons in conditions in which motivation and emotion dominated indicates that the differentiated motivational and emotional hypothalamic influences in cortical processes during learning are mediated via the coordinated activity of neurons in the motivational and reinforcing systems of the hypothalamus.

Animals↗

Transmitter mediated arginine vasopressin release from superfused hypothalamus and pituitary gland.

The study was designed to investigate the effect of various neurotransmitters on the hypothalamus and pituitary gland to determine the sites of their action. Superfused isolated rat hypothalami and pituitary glands demonstrated basal secretion of arginine vasopressin (AVP) and repeated response to stimulation thus showing the viability of the preparation. Acetylcholine and histamine stimulated the release of AVP at the hypothalamic and pituitary levels; dopamine and norepinephrine released AVP in a dose related manner only from the hypothalamus; angiotensin II released AVP in the same fashion only from the pituitary gland. AVP secretion stimulated by dopamine and norepinephrine may represent synaptic inputs which are localized at the hypothalamus and must be distinguished from the site of action at the pituitary gland of angiotensin II.

Acetylcholine↗

Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer's disease patients: amorphic plaques and cytoskeletal changes occur independently.

Alzheimer's disease is characterized neuropathologically by senile plaques and cytoskeletal changes. It has been proposed that amorphic plaques would locally induce anterograde propagation of cytoskeletal changes in consecutive neurons followed by amorphic plaque deposition at their axonal terminals. The Alzheimer changes would spread in this way along neural pathways. To test the 'primary amyloid anatomical cascade hypothesis', Congo red staining, beta-protein/A4 (Abeta) antiserum and Alz-50, which recognizes cytoskeletal changes, were applied to the hypothalamus and adjoining brain areas of five Alzheimer's disease patients of 40-90 years of age and five age- and sex-matched controls. The results showed that (1) virtually all Abeta plaques in the hypothalamus were of the Congo red-negative amorphic type; (2) amorphic plaques and Alz-50-stained cytokeletal changes were observed not only in all Alzheimer's disease patients but also in a non-demented, 90-year-old control subject; (3) the density of amorphic plaques in the hypothalamus was unrelated to the duration of the dementia; (4) the density of amorphic plaques was unrelated to that of Alz-50-stained cytoskeletal changes; (5) double-labeling with anti-Abeta and Alz-50 did not show an evident topical relationship between amorphic plaque deposition and the occurrence of cytoskeletal changes; and (6) the distribution of Abeta and Alz-50 staining in five brain areas, for which essential anatomical information is available, did not support the primary amyloid anatomical cascade hypothesis. Amorphic plaques and cytoskeletal changes rather occur independently.

Adult↗

Apoptotic signaling proteins: possible participation in the regulation of vasopressin and catecholamines biosynthesis in the hypothalamus.

The role of apoptotic signaling proteins for long-lived neurons in the mature brain is poorly understood. Recently, we have shown that water deprivation leads to the activation of vasopressin (VP) secretion and expression of Bcl-2 and caspase-9 apototic proteins in the hypothalamus of the rat brain. In the present work, we continued to study a possible relationship between the functional activity of neurosecretory cells of the hypothalamus and apoptosis related proteins. We found that water deprivation leads to simultaneous activation of synthesis of VP and p53 and Bcl-2 apoptotic proteins in the mouse brain. To study a possible effect of apoptotic proteins on the functional state of hypothalamic neurons, the VP and tyrosine hydroxylase (TH) synthesis were analyzed in p53, p21(Waf1/Cip1) and Bcl-2 deficient mice. Loss of p53 and Bcl-2 significantly reduced VP synthesis in paraventricular and supraoptic nuclei and TH expression in arcuat, periventricular and zona incerta nuclei of the hypothalamus. Surprisingly, in contrast with the loss of p53, the inactivation of p21(Waf1/Cip1) up-regulates the expression of VP and TH. These data indicate that p53, p21(Waf1/Cip1) and Bcl-2 proteins, besides affecting cell cycle, tumor suppression and apoptosis, may act as modulators of neurosecretory activity of hypothalamic neurons; however, this problem remains to be determined more detailed.

Animals↗

Axonal projections from the hypothalamus to the median eminence in rats during ontogenesis: DiI tracing study.

This study has determined the ontogenetic schedule of the arrival of the axons from the hypothalamus and the diagonal band in the median eminence in rats by using the fluorescent lipophilic carbocyanine dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a retrograde tracer. After fixation of the brain, the crystals of the dye were implanted in the median eminence on the 13th, 14th, 15th, 16th, 17th, 20th embryonic days, and on the 2nd postnatal day. This was followed by fluorescent staining of the neuronal cell bodies in the hypothalamus. According to our data, the axons of rare hypothalamic neurons first reached the primordium of the median eminence on the 14th embryonic day. For two subsequent days, the number of neurons projecting the axons to the median eminence appeared to increase considerably. They were widely distributed through the hypothalamus and in the ventromedial region of the more rostral forebrain. Till the 20th embryonic day, the majority of the fluorescent neurons were concentrated mainly in the paraventricular nucleus (dorsal and medial parts) and the arcuate nucleus, and to a lesser extent in the medial preoptic nucleus, the supraoptic nucleus, the diagonal band, and the retrochiasmatic nucleus. In neonates, DiI-labelled neurons appeared additionally in the accessory dorsolateral nucleus, medial preoptic area lateral to the diagonal band, anterior hypothalamic area, and in the anterior periventricular nucleus. Thus, the axons of differentiating neurons arrive in the median eminence from the 14th embryonic day till the neonatal period, providing the pathway for the neurohormone transfer to the hypophysial portal circulation.

Animals↗

[Deep brain stimulation in the posterior hypothalamus for chronic cluster headache. Case report and review of the literature].

Primary chronic cluster headache (CCH) is a rare but severe pain syndrome and pathophysiological explanations are still missing. PET studies revealed activation in the hypothalamus and therefore it became a target for therapeutic deep brain stimulation (DBS). A case of a 39-year-old woman and a literature review are presented. The patient suffered from left-sided primary CCH for 14 months. The headache was resistant to any pharmacological therapy or treatment was limited by major drug side effects. Using a stereotactic approach a quadripolar lead was inserted in the left posterior hypothalamus. A test trial was performed and attack frequency, intensity, and adverse events were noted. Intraoperative test stimulation evoked typical side effects like tachycardia, diplopia and panic attacks. During the trial test a marked reduction in frequency and intensity of CCH was recorded. After 7 days the stimulation device was implanted subcutaneously. DBS with implantation of a lead in the ipsilateral inferior posterior hypothalamus is an experimental treatment option and should be offered to selected patients in a prospective controlled clinical trial. Data concerning the long-term follow-up need to be collected.

Adult↗

Aromatase inhibition abolishes courtship behaviours in the ring dove (Streptopelia risoria) and reduces androgen and progesterone receptors in the hypothalamus and anterior pituitary gland.

The aim of this study was to determine in the ring dove, the effects of aromatase inhibition on the expression of aggressive courtship and nest-soliciting behaviours in relation to the distribution of cells containing immunoreactive androgen (AR) and progesterone (PR) receptor in the hypothalamus and pituitary gland. Isolated sexually experienced ring doves were transferred in opposite sex pairs to individual breeding cages, and then injected with the aromatase inhibitor, fadrozole (four males and four females), or saline vehicle (four males and four females) for 3 days at 12 hourly intervals. Saline-injected control males displayed aggressive courtship behaviours (bow-cooing and hop-charging) and nest-soliciting throughout the study, and control females displayed nest-soliciting. By day 3, fadrozole treatment resulted in the disappearance of all these behaviours and in a decrease or disappearance of AR and PR in the anterior pituitary gland, and in the nucleus preopticus paraventricularis magnocellularis (PPM), nucleus preopticus medialis (POM), nucleus hypothalami lateralis posterioris (PLH), and ventral, lateral and dorsal nucleus tuberalis in the hypothalamus (VTu, LTu, DTu). In the nucleus preopticus anterior (POA), fadrozole treatment decreased AR in both sexes and decreased PR in females but not in males. Cells containing co-localized nuclear AR and PR were found in all hypothalamic areas examined, and in the anterior pituitary gland. Fadrozole is suggested to reduce the local availability of estrogen required indirectly for the induction of AR, and except in cells containing PR in the male POA, for the direct induction of PR. It is suggested that aggressive courtship behaviour is terminated by "cross talk" between aromatase-independent PR and aromatase-dependent AR co-localized in neurons in the POA. Aromatase-independent PR may increase in the male POA in response to visual cues provided by a partner. Aromatase-dependent PR in the POM, and basal hypothalamus may play a role in the facilitatory effect of progesterone on estrogen-induced nest-orientated behaviours.

Animal Communication↗

Immunohistochemical distribution and subcellular localization of the somatostatin receptor subtype 1 (sst1) in the rat hypothalamus.

The aim of the present study was to examine the cellular and sub-cellular distribution of the somatostatin (SRIF) receptor subtype sst1 in the rat hypothalamus. Receptors were immunolabeled using an antibody directed against an antigenic sequence in the N-terminus of the receptor. Immunopositive neuronal cell bodies and dendrites were observed throughout the mediobasal hypothalamus, including the medial preoptic area, paraventricular, periventricular, and arcuate nuclei. Immunoreactive axons and axon terminals were also observed in the median eminence, suggesting that sst1 is also located pre-synaptically. Electron microscopic examination of the arcuate nucleus revealed a predominant association of immunoreactive sst1 with perikarya and dendrites. Most immunoreactive receptors were intracellular and localized to tubulovesicular compartments and organelles such as the Golgi apparatus, but 14% were associated with the plasma membrane. Of the latter, 47% were apposed to abbuting afferent axon terminals and 20% localized immediately adjacent to an active synaptic zone. These results demonstrate a widespread distribution of sst1 receptors in rat hypothalamus. They also show that somatodendritic sst1 receptors in the arcuate nucleus are ideally poised to mediate SRIF's modulation of afferent synaptic inputs, including central SRIF effects on growth hormone-releasing hormone neurons documented in this area.

Animals↗

Changes in LH-releasing hormone content of the hypothalamus and electron microscopy of the anterior pituitary after prostaglandin E2 injection in rats.

The purpose of this study is to present evidence that prostaglandin (PG) E2 stimulates a release of luteinizing hormone-releasing hormone (LH-RH) from the hypothalmus. In experiment 1, 72 hours after estrogen and progesterone treatment, a solution of 700 mug of PGE2 was injected into the jugular vein. Blood samples for plasma LH and the hypothalamus for LH-RH assay were collected before and 5, 10, and 30 minutes after PGE2 injection and subjected to radioimmunoassay. The total LH-RH content of the hypothalamus decreased from 20.4 to 15.3 ng. at 5 minutes after PGE2 and had returned to the pretreatment level by 30 minutes after PGE2 administration. On the other hand, plasma LH levels increased at 5 minutes, reached a peak at 10 minutes, followed by a decline at 30 minutes after PGE2 injection. In Experiment 2, 10 and 30 minutes after a single injection of PGE2 or synthetic LH-RH, the anterior pituitary were excised for an electromicroscopic study. Ten minute after PGE2, an enlarged Golgi apparatus, well-developed rough endoplasmic reticulum, and decreased secretory granules were observed in pituitary gonadotropins as compared with the control group. These changes were more conspicuous in the pituitaries obtained 30 minutes after PGE2. In Experiment 3, plasma LH levels were determined serially before and 10, 30, 60, and 90 minutes after a single injection of PGE2, LH-RH, or saline. There is a striking resemblance between the PGE2- and LH-RH-treated groups. Plasma LH levels in both these groups reached a peak at 10 minutes and started to decline 30 minutes after PGE2 or LH-RH administration. Our findings would indicate that PGE2 stimulates LH-RH secretion from the hypothalamus.

Animals↗

Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay.

A rapid and reproducible radioimmunoassay method was developed for rat atrial natriuretic factor (ANF)-IV. The method is also applicable to human atrial peptide. ANF was detected in rat hypothalamus (5.03 pmoles/g tissue), right (86.8 pmoles/mg tissue) and left atria (52.5 pmoles/mg tissue), and plasma (156 fmoles/ml). After high salt intake immunoreactive ANF in atria and plasma increased significantly, while a significant decrease was observed in hypothalamus. Gel chromatography revealed high and low molecular weight ANF in atria and hypothalamus while only a low molecular weight form was found in plasma.

Amino Acid Sequence↗

Differential effect of benserazide on catecholamine concentrations in the rat pineal, cerebral cortex and hypothalamus.

The effect of benserazide, an aromatic L-amino acid decarboxylase inhibitor, has been investigated simultaneously on the noradrenaline content of the pineal, hypothalamus and cerebral cortex of the rat. The dopamine concentration of the hypothalamus was investigated in the same animals. Benserazide had no effect on pineal noradrenaline content throughout the light phase and the early part of the dark phase but caused a drastic reduction in the latter part of the dark period. The drug had no significant effect on noradrenaline or dopamine contents of the hypothalamus. Benserazide treatment caused a large reduction in the noradrenaline content of the cerebral cortex throughout 24 hr. However, this effect is unlikely to be due to a differential penetration of benserazide into the brain areas as a similar degree of decarboxylase inhibition was observed in all three tissues.

Animals↗

Unit activities in the hypothalamus and midbrain during stimulation of hypothalamic attack sites.

Unit activity in the hypothalamus and midbrain of unanesthetized cats was studied during electrical stimulation of the hypothalamus at sites that induced attack and at other comparable sites from which attack was not induced. The changes in the firing of units at distances from 0.7 to 1.9 mm from the site of stimulation were similar to those of units at distances from 2.0 to 5.2 mm. Although stimulation in general affected a majority of units, resulting in increases rather than in decreases of firing rates, and produced similar patterns of unit activity, stimulation at sites that induced attack affected more units, produced a greater change in unit activity and markedly increased firing rates in the lateral hypothalamus and the dorsal part of the midbrain.

Aggression↗

The effect of trauma on the formaldehyde-induced fluorescence of noradrenaline in the hypothalamus and brain stem of the rat.

Noradrenaline (NA) fluorescence in the hypothalamus and brain stem of the rat has been examined during and up to 1.5 h after a 4-h period of bilateral hind-limb ischaemia. A decrease in the fluorescence of the NA terminals in the n. supraopticus and n. paraventricularis was seen during the second half of the period of limb ischaemia and became more marked 1.5 h after removal of the tourniquets. Changes in the preoptic-anterior hypothalamic (POAH) area and n. dorsomedialis occurred more slowly and depletion was best seen after the limb ischaemia. Measurements of the fluorescence with a microphotometer confirmed the changes seen in the POAH area, the n. supraopticus and the n. dorsomedialis 1.5 h after 4 h bilateral hind-limb ischaemia but suggested that the visual gradings of changes in the n. paraventricularis, which normally has a high NA content, could be unreliable. No changes were seen at any of the times studied in the ventral part of n. striae terminalis. The cells of origin of the affected terminals could not be identified since no changes were detected in the fluorescence of the cells in the NA nuclei of the brain stem. alpha-Methyl-p-typrosine, given at the start of the experiment to inhibit tyrosine hydroxylase, reduced the fluorescence of these cells but still no difference could be discerned between those in the control and injured rats. These results confirm the previous chemical findings of a fall in the NA concentration in the hypothalamus after injury with little change in that of brain stem. The results are discussed in relation to the effects of the injury on the homoeostatic functions of the hypothalamus.

Animals↗

Effect of prostaglandin, pyrogen and noradrenaline, injected into the hypothalamus, on thermoregulation in newborn lambs.

Thirteen newborn lambs were implanted stereotaxically with an array of 4 guide tubes positioned bilaterally so that their tips lay above various hypothalamic loci. At postnatal ages 50-70 h, rectal temperature was monitored, and bilateral 1 microliter injections were made into the hypothalamus. Prostaglandin E1 (0.2 microgram) and prostaglandin E2 (0.2-2.0 microgram) did not cause fever on any occasion though injections were made into 44 sites throughout the hypothalamus. Nevertheless, lambs that did not develop fever following central injection were often, if sensitized by bacterial pyrogen given earlier able to develop fever after intravenous injection of bacterial pyrogen. Infusion of a bacterial pyrogen (S. abortus equi, 0.2 microgram) into these same sites caused fever only when injections were made into the anterior hypothalamic/preoptic area (AH/POA). Eight lambs were placed in a 10 degrees C environment and noradrenaline was injected. Rectal temperature fell by 0.5-1.4 degrees C after 7 bilateral injections into the AH/POA, but 9 injections into other hypothalamic areas caused little temperature change. When 6 lambs were placed at a temperature of 30 degrees C and noradrenaline was injected, no consistent temperature changes were observed after microinjection into the AH/POA or other parts of the hypothalamus.

Animals↗