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PubMed2003

Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats.

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.

Animals↗
PubMed1998

Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARH) and dorsomedial nucleus (DMH), areas activated during lactation, project to the paraventricular nucleus of the hypothalamus (PVH).

Lactation induces an increase in NPY activity in two neuronal populations in the hypothalamus: the arcuate nucleus (ARH) and the dorsomedial nucleus (DMH) area. To determine if NPY neurons from these areas project to the paraventricular nucleus of the hypothalamus (PVH), the retrograde tracer, fluorogold (FG), was injected into the PVH of lactating females. FG-labeled NPY cells (identified by in situ hybridization for NPY mRNA) were observed throughout the ARH; however, a greater number of double-labeled cells were found in the caudal portion than the rostral portion of the ARH. Thus, NPY neurons in the caudal portion of the ARH provide the major ARH NPY input into the PVH area. If these results are combined with our previous data showing that activation of NPY neurons in the ARH during lactation is confined to the caudal portion, it is very likely that the lactation-activated NPY neurons project to the PVH. FG-labeled NPY cells were also identified in the DMH area, providing the first evidence that the NPY neurons in the DMH area activated during lactation also project to the PVH. Taken together, the increase in NPY activity may be important in modulating some of the physiological alterations occurring during lactation, such as the increase in food intake, in part through modulating PVH neuronal activity.

Animals↗
PubMed1999

Lateral evaginations from the third ventricle into the rat mediobasal hypothalamus: an amplification of the ventricular route.

In this work we report the existence of several evaginations extending out of the third ventricle within the mediobasal hypothalamus of the rat. In coronal sections, these evaginations appear as very narrow canaliculi integrating a canalicular system, which increases the contact surface between the ventricular lining and the nervous tissue. Consequently these evaginations enlarge the ventricular route for the transport of active principles present in the cerebrospinal fluid, such as (neuro)hormones and neurotransmitters. The mediobasal hypothalamus includes the arcuate nucleus and the median eminence (both involved in neuroendocrine mechanisms and in the regulation of pituitary function). A possible implication of our finding is that the neuroactive substance-containing ventricular cerebrospinal fluid may reach the intercellular spaces of the surrounding neuropil of the arcuate nucleus. According to literature these substances cross the ependyma of the lateral wall of the infundibular recess of the third ventricle. We suggest that such substances might also pass through the ependymal lining of the canalicular system, which displays the same ultrastructural characteristics as the rest of the ependyma of the lateral wall of the third ventricle. Therefore, the arcuate neurons may be influenced not only by synaptic inputs (afferent fibers) but also by non-synaptic diffusion neurotransmission (by means of neuroactive substances present in the cerebrospinal fluid).

Animals↗
PubMed1990

Locomotor stepping initiated by glutamate injections into the hypothalamus of the anesthetized rat.

Glutamate (50 mM, 50 nl) injected into the tuberal and posterior hypothalamus was tested for capacity to elicit locomotor stepping. Rats (n = 23) were anesthetized with Nembutal and suspended by a sling in a stereotaxic apparatus such that locomotor stepping rotated a wheel. In 61 of 275 sites tested, stepping was initiated by glutamate injections within 60 s. Positive sites were widespread and contained in the lateral hypothalamus, the perifornical area, the dorsomedial nucleus, and the zona incerta. The perifornical and lateral hypothalamic sites were most likely to have locomotor responses and the shortest latencies. These findings indicate that selective activation of hypothalamic neurons as opposed to fibers of passage can initiate locomotion.

Animals↗
PubMed1996

Expression of fos-like immunoreactivity in the hypothalamus of the ring dove (Streptopelia risoria) at the onset of incubation.

Fos immunocytochemistry was used in the ring dove (Streptopelia risoria) to identify areas in the forebrain and hypothalamus which might be involved in the expression of incubation behaviour and the associated changes in neuroendocrine function. In this species, both sexes participate in incubation which becomes fully established after laying the second egg in the two egg clutch. The eggs hatch after 14-15 days incubation. Observations were made in both sexes 16-18 h after laying the first egg, 3-5 h after laying the second egg, and after 12-14 days of incubation. Non-breeding birds were used as controls. Fos-labelled cells were observed in several forebrain areas in both sexes irrespective of reproductive status but their numbers did not change during incubation. In the hypothalamus, very few fos-labelled cells were seen in non-breeding birds but appeared in both sexes in the nucleus preopticus medialis after egg laying and after 12-14 days of incubation. Fos-labelled cells also appeared in the nucleus tuberis (=arcuate nucleus) in both sexes after laying the first or second egg and less abundantly, after 12-14 days incubation. Additionally, in males only, fos-labelled cells were seen after the laying of the first and second eggs in the rostral area of the nucleus tuberis close to the walls of the third ventricle. These observations suggest that the fos-labelled cells in the nucleus preopticus medialis may be involved in the expression of incubation behaviour while those in the nucleus tuberis may be involved in the regulation of gonadotrophin or prolactin secretion.

Animals↗
PubMed1999

Hypothalamic involvement in the regulation of maternal behaviour in the rat: inhibitory roles for the ventromedial hypothalamus and the dorsal/anterior hypothalamic areas.

The present report examines the possible involvement of the ventromedial hypothalamus (VMH), the dorsal hypothalamus (DH), and the anterior hypothalamic area (AHA) in the regulation of maternal behaviour in the female rat. In a series of experiments it was found that either infusions of saline or lowering cannulas into the VMH stimulated a rapid onset of maternal behaviour in progesterone plus oestrogen-primed, nulliparous rats. The stimulatory effect of cannula lowering into the VMH on maternal behaviour was shown to be steroid-dependent. Next, the involvement of cell bodies located in the DH/AHA in maternal behaviour was examined after bilateral lesions of these regions with the neurotoxin, N-methyl-D-aspartic acid (NMA). NMA lesions of the DH/AHA stimulated a rapid onset of maternal behaviour in oestrogen-treated, nulliparous rats, while NMA lesions in non-steroid-treated animals or vehicle infusions in steroid or non-steroid-treated rats failed to induce a rapid onset of behaviour. In a final study the effects of NMA lesions of the VMH were evaluated. As in AHA lesioned rats, NMA lesions of the VMH stimulated a fast onset of maternal behaviour in steroid-primed females. These findings indicate that the VMH as well as the DH/AHA exert chronic steroid-dependent inhibitory influences on the induction of maternal behaviour.

Animals↗
PubMed1999

Leptin sensitive neurons in the hypothalamus.

A major paradigm in the field of obesity research is the existence of an adipose tissue-brain endocrine axis for the regulation of body weight. Leptin, the peptide mediator of this axis, is secreted by adipose cells. It lowers food intake and body weight by acting in the hypothalamus, a region expressing an abundance of leptin receptors and a variety of neuropeptides that influence food intake and energy balance. Among the most promising candidates for leptin-sensitive cells in the hypothalamus are arcuate nucleus neurons that co-express the anabolic neuropeptides, neuropeptide Y (NPY) and agouti-related peptide (AGRP), and those that express proopiomelanocortin (POMC), the precursor of the catabolic peptide, alphaMSH. These cell types contain mRNA encoding leptin receptors and show changes in neuropeptide gene expression in response to changes in food intake and circulating leptin levels. Decreased leptin signaling in the arcuate nucleus is hypothesized to increase the expression of NPY and AGRP. Levels of leptin receptor mRNA and leptin binding are increased in the arcuate nucleus during fasting, principally in NPY/AGRP neurons. These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling, and that the arcuate nucleus is an important target of leptin action in the brain.

Agouti-Related Protein↗
PubMed1980

A role of the rostral hypothalamus in the regulation of LHRH release in baboons.

In the intact control baboons the plasma level of LH was elevated and reached a peak within 15 minutes after administration of 100 microgram synthetic LHRH. In addition, a second peak in plasma LH appeared within 90 minutes after LHRH injection. Supplementing these results, plasma level of estrogen was elevated within 30 minutes after LHRH injection. Subsequently, frontal deafferentation of the hypothalamus was performed in these baboons. After administration of 100 microgram synthetic LHRH in these frontally deafferented baboons the plasma level of LH was elevated and reached a peak within 15 minutes, as in the intact control baboons. However, there was no second LH peak within 90 minutes after LHRH injection, even though plasma estrogen was elevated within 30 minutes, as in the intact control baboons. It was found that the rostral hypothalamus in baboons is involved in the regulation of LHRH release which promotes to release LH within 90 minutes after LHRH injection.

Animals↗
PubMed2002

Influence of estradiol on NADPH diaphorase/neuronal nitric oxide synthase activity and colocalization with progesterone or type II glucocorticoid receptors in ovine hypothalamus.

Nitric oxide (NO) has been shown to play an important role in both the neuroendocrine reproductive and stress axes, which are closely linked. Because progesterone (P4) receptors (PRs) and glucocorticoid receptors (GRs) are not found in GnRH neurons and the NOergic system has been implicated in the control of GnRH secretion, this study aimed to ascertain whether steroids altered the NOergic system. Our first objective was to map the distribution of NO synthase (NOS) cells in the ovine preoptic area (POA) and hypothalamus and to determine whether NOS activity is enhanced by estradiol (E2) treatment. Using NADPH diaphorase (NADPHd) histochemistry, we found that NADPHd-positive neurons were spread throughout the ovine POA and hypothalamus, and that all NADPHd cells were immunoreactive for NOS. In response to estradiol, a significant increase in the number of NADPHd cells was noted only in the ventrolateral region of the ventromedial nucleus (VMNvl), with no significant difference in the POA or arcuate nucleus. Progesterone and glucocorticoid receptors were colocalized with NADPHd reactive neurons in the POA, arcuate nucleus, and VMNvl of ewes in both treatment groups. In ewes receiving estradiol, the number of NADPHd-positive cells containing steroid receptors in the POA (PR, 81%; GR, 79%) and arcuate nucleus (PR, 89%; GR, 84%) was similar, but in the VMNvl, fewer NADPHd-positive cells contained GR (PR, 88%, GR, 31%). These data show that estradiol up-regulates NOS activity in a site-specific manner and that the influence and possible interaction of progesterone and corticosteroids on NO producing cells may differ according to the neural location.

Animals↗
PubMed1993

Expression of growth hormone receptor gene in rat hypothalamus.

Growth hormone receptor (GHR) mRNA-expressing cells in the hypothalamus were observed using hybridization histochemistry in adult male rats. Digoxigenin-labeled cRNA corresponding to the extracellular part of rat GHR was used as a probe. Northern blotting analysis of hypothalamic total RNA from adult male rats revealed that the 4.5 kilobase (kb) transcript of the GHR gene corresponding to the GHR messenger RNA (mRNA) predominated over the 1.2 kb transcript corresponding to GH-binding protein mRNA. GHR mRNA-containing cells were observed in the arcuate nucleus (ARC), the periventricular nucleus (PeV), ventrolateral region of the ventromedial nucleus, the paraventricular nucleus and the supraoptic nucleus. To further understand the significance of the GHR gene expression in the hypothalamus, the effect of in vivo manipulation of GH on the somatostatin (SS) gene expression in the ARC and PeV, and the GRF gene expression in the ARC was observed among adult male rats using in situ hybridization histochemistry. Ten days after hypophysectomy, the SS mRNA level in the ARC as well as PeV was significantly lower than that in the respective nuclei of sham-operated control rats, while the GRF mRNA level in the ARC was significantly higher than that in the ARC of control animals. Subcutaneous injection of recombinant human GH (0.33 mg) to hypophysectomized rats every 12 h for 5 days restored the SS mRNA level in the ARC and PeV, and reduced the GRF mRNA level in the ARC to that of control animals. The data suggest that GH directly acts on the hypothalamic PeV and ARC, and alters the gene expression of SS and GRF.

Animals↗
PubMed1975

Optimal parameters for eliciting cardio-acceleration by electrical stimulation of the ventromedial hypothalamus.

The ventromedial hypothalamus of the unrestrained cat was stimulated electrically through permanent electrodes. The stimulation parameters, amplitude, duration and frequency of the square wave pulses were combined to produce a 20% increase of the resting heart rate value. The total electric charge for each parametric combination was calculated. The charge per stimulation (10 s) varied from about 1 to 100 micro-coulombs, depending on the parametric combination used. The response could therefore not be expressed as a function of the charge but depended on the individual parametric combinations. The relation among the stimulation parameters and the total amount of electric charge of the pulses was estimated by the correlation technique. The results suggested that about 60% of the variation in the electric charge resulting in the constant response was due to the variation of the pulse repetition frequency. The optimal parameters for eliciting cardio-acceleration in the cat by stimulation of the ventromedial hypothalamus seem to be pulse durations between 0.1 and 0.5 ms and pulse repetition frequencies below 100 P/s, with pulse amplitude as the dependent variable.

Animals↗
PubMed2001

Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus.

We report the development of a pseudorabies virus that can be used for retrograde tracing from selected neurons. This virus encodes a green fluorescent protein marker and replicates only in neurons that express the Cre recombinase and in neurons in synaptic contact with the originally infected cells. The virus was injected into the arcuate nucleus of mice that express Cre only in those neurons that express neuropeptide Y or the leptin receptor. Sectioning of the brains revealed that these neurons receive inputs from neurons in other regions of the hypothalamus, as well as the amygdala, cortex, and other brain regions. These data suggest that higher cortical centers modulate leptin signaling in the hypothalamus. This method of neural tracing may prove useful in studies of other complex neural circuits.

Afferent Pathways↗
PubMed1984

Vasopressin injected into the hypothalamus triggers a stereotypic behavior in golden hamsters.

Microinjection of arginine vasopressin into the medial preoptic area of the hypothalamus of male and female golden hamsters triggered a complex, stereotypic behavior--flank marking--a type of scent marking used in olfactory communication. The flank marking was not elicited by saline, oxytocin, neurotensin, or angiotensin II. Vasopressin was ineffective when injected into other areas of the hypothalamus or into the lateral cerebroventricle.

Angiotensin II↗
PubMed1978

Sodium intake following destruction of the anterior hypothalamus in the rat.

Sodium intake and sodium output were measured in rats before and after lesioning of the anterior hypothalamus. Both parameters were lower than control rats following the lesioning procedure. When an amount of sodium was given orally to these lesioned rats to make up the deficit in sodium intake, no difference was found in sodium intake or output between the rats with lesions and normal rats. Rats with anterior hypothalamic lesions were able to increase their sodium intake following a period of sodium deprivation or adrenalectomy. When presented with concentrations of sodium chloride ranging between 0.9 and 2.5% rats with lesions decreased their intake of sodium in a manner similar to control rats except that the level of intake in the lesioned rats was lower for all concentrations. Control rats and those with lesions were not different in their intakes of KC1 solutions. These findings suggest that the anterior hypothalamus is important in setting the absolute intakes of sodium but does not interfere with the control mechanisms regulating the sodium intake.

Adrenalectomy↗
PubMed1996

Basal and glucoprivic-induced changes in extracellular GABA in the ventral hypothalamus of Zucker rats.

The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.

Animals↗
PubMed2002

Regulation of prolactin secretion by dopamine at the level of the hypothalamus in the turkey.

Avian prolactin (PRL) secretion is regulated by vasoactive intestinal peptide (VIP) neurons residing in the infundibular nuclear complex (INF) of the hypothalamus. This VIPergic activity is modulated by stimulatory dopaminergic inputs. Dynorphin, serotonin (5-HT), dopamine (DA) and VIP all appear to stimulate PRL secretion along a hypothalamic pathway, expressing kappa opioid, serotonergic, dopaminergic and VIPergic receptors in succession, with the VIPergic system as the final mediator. Electrical stimulation (ES) within the turkey hypothalamus at the level of the medial preoptic area (POA), the ventromedial hypothalamic nucleus (VMN), the INF or the median eminence (ME) results in the release of PRL. When the selective D(1) DA receptor antagonist SCH-23390 HCl was infused intraventricularly at the rate of 10 nmol/min, ES in the POA or VMN was unable to increase PRL levels, while ES in the INF and ME did increase PRL to the same level as that of controls. These results were interpreted to suggest that the D(1) DA receptors involved in PRL release lie caudally to the VMN and dorsally to the INF. Bilateral microinjections (50 ng) of the D(1) DA receptor agonist SKF-38393 HCl into the POA or VMN failed to produce any increase in PRL, while similar microinjections in the INF increased PRL significantly within 15 min. Bilateral microinjections of the D(1) DA antagonist (50 ng) into the INF blocked the rise in PRL associated with ES in the POA. Bilateral microinjections of a D(2) DA antagonist (50 ng) into the INF failed to block PRL secretion induced by ES in the POA. Tract tracing, using double-label immunocytochemistry, revealed the presence of a monosynaptic dopaminergic pathway projecting from the POA to the INF. These data imply that the only hypothalamic D(1) DA receptors involved in the regulation of avian PRL secretion are those residing within the INF in the same region as the VIP neurons known to be involved in PRL secretion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Transcription factor STAT3 in leptin target neurons of the rat hypothalamus.

Leptin is an adipose tissue-derived hormone that regulates body weight via interactions with hypothalamic neuronal circuitries expressing specific leptin receptors (Ob-R). The Ob-Rs act via the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway of signal transduction. Recent evidence suggests that primarily the transcription factor STAT3 mediates leptin's action in the hypothalamus. We have investigated the presence and cellular localization of STAT3 protein in the rat hypothalamus by means of indirect immunofluorescence histochemistry using a rabbit polyclonal STAT3 antiserum. The antiserum identified a 92-kDa protein using Western blotting on rat hypothalamic homogenates, corresponding to the expected size of STAT3. STAT3 immunoreactivity was demonstrated in Ob-R-containing neurons of the paraventricular nucleus (parvocellular part), periventricular nucleus, arcuate nucleus and in the lateral hypothalamic area. Direct double-labeling showed presence of STAT3 immunoreactivity in neuropeptide Y (NPY)-containing neurons of the ventromedial part of the arcuate nucleus and in proopiomelanocortin (POMC)-containing neurons of the ventrolateral part of the arcuate nucleus. The results provide an anatomical basis for a leptin action mediated by STAT3 in Ob-R-containing NPY and POMC neurons of the arcuate nucleus, as well as by Ob-R-containing neurons of the parvocellular paraventricular nucleus and lateral hypothalamic area.

Animals↗
PubMed2000

Differential orexigenic effects of hexarelin and its analogs in the rat hypothalamus: indication for multiple growth hormone secretagogue receptor subtypes.

We have previously reported that hexarelin and some of its analogs, including EP 50885, stimulated GH secretion and feeding after systemic administration in the rat, whereas EP 40904 selectively stimulated food intake and EP 40737 only GH release. The precise mechanism of growth hormone-releasing peptides (GHRPs) actions is still unclear, but the integrity of the arcuate nucleus of the hypothalamus (ARC) appears crucial for their endocrine effects. To better characterize the site(s) and mechanisms(s) of the orexigenic action of GHRPs, we have investigated their effects after infusion into the arcuate, paraventricular, ventromedial and medial preoptic areas of the hypothalamus. Food intake was measured for 60 min following injection of the test compound (2 microg/rat). Hexarelin, EP 40904 and EP 50885 had significant orexigenic effects after injection into the ARC. A specific NPY antagonist significantly inhibited the effect of hexarelin, whereas a GHRH antagonist was ineffective. In the paraventricular nucleus, only EP 50885 stimulated feeding, whereas all peptides were ineffective in the ventromedial nucleus and medial preoptic area. Taken altogether, these results demonstrate that GHRPs are endowed with site-specific orexigenic actions and that endogenous NPY, but not GHRH, mediates these effects. The additional orexigenic action of EP 50885 in the paraventricular nucleus suggests the existence of a GHRP receptor subtype different from the already cloned one.

Animals↗