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PubMed1996

Distribution of pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactivity in the hypothalamus and extended amygdala of the rat.

Pituitary adenylate cyclase activating polypeptide (PACAP) is found in two forms of 27 and 38 amino acids (PACAP-27 and PACAP-38 respectively) in the mammalian central nervous system. Using antibodies to these two forms of PACAP, we examined the distribution of PACAP immunoreactivity in the rat hypothalamus and a number of extrahypothalamic areas. The patterns of immunostaining for PACAP-27 and PACAP-38 were similar: prominent terminal labelling was present in the retrochiasmatic area, median eminence, and posterior periventricular nucleus of the hypothalamus as well as the bed nucleus of the stria terminalis and amygdaloid complex. After colchicine treatment, immunopositive cell bodies were found in the preoptic region of the periventricular zone of the hypothalamus, the suprachiasmatic and paraventricular hypothalamic nuclei, neural structures adjacent to the median eminence (including the retrochiasmatic area, arcuate nucleus, ventromedial hypothalamus, and tuber cinereum), and the lateral mammillary and supramammillary nuclei. In all these areas, immunolabelling appeared specific since it was abolished by preabsorption of primary antisera with the appropriate PACAP peptide. However, the number of immunopositive cells in the suprachiasmatic nucleus was also reduced by preabsorption of PACAP-27/38 antisera with vasoactive intestinal polypeptide, suggesting that a subpopulation of cells in the suprachiasmatic nucleus express a peptide which has significant sequence homology with both PACAP-27/38 and vasoactive intestinal polypeptide. The distribution of PACAP immunoreactivity throughout the hypothalamus, bed nucleus of the stria terminalis, and amygdala suggests the involvement of PACAP in a number of processes including limbic, autonomic, and neuroendocrine functions as well as regulation of the circadian pacemaker.

Amygdala↗
PubMed1997

Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain.

In situ hybridization histochemistry was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) genes in the human hypothalamus and basal forebrain. Hypothalami from five adult males were frozen in isopentane at -30 degrees C and serially sectioned at 20 jm thickness. Every 20th section was hybridized with [35S]-labeled, 48-base synthetic cDNA probes that were complementary to either SP or NKB mRNAs. Slides were dipped into nuclear emulsion for visualization of mRNAs at the single-cell level. The location of labeled neurons (greater than x 5 background) was mapped by using an image-combining computer microscope system. A distinct and complementary distribution pattern of SP and NKB neurons was observed in the human hypothalamus and basal forebrain. NKB was the predominant tachykinin in the rostral hypothalamus, whereas SP mRNA predominated in the posterior hypothalamus. Numerous NKB neurons were identified in the magnocellular basal forebrain, the bed nucleus of stria terminalis, and the anterior hypothalamic area. Scattered NKB neurons were present in the infundibular and paraventricular nuclei, paraolfactory gyrus, posterior hypothalamic area, lateral division of the medial mammillary nucleus, and amygdala. Numerous neurons expressing SP mRNAs were identified in the premammillary, supramammillary, and medial mammillary nuclei; the posterior hypothalamic area; and the corpus striatum. Scattered SP neurons were also observed in the preoptic area; the infundibular, intermediate, dorsomedial, and ventromedial nuclei; the infundibular stalk; the amygdala; the bed nucleus of stria terminalis; and the paraolfactory gyrus. These studies provide the first description of the location of neurons that express tachykinin gene transcripts in the human hypothalamus.

Adolescent↗
PubMed1992

Peptidergic neurotransmitters in the endocrine hypothalamus.

More than 20 neuropeptides have been localized in the endocrine hypothalamus. They may exert a neurohormonal effect on the pituitary or innervate other neurons (intranuclear, intrahypothalamic or extrahypothalamic) and act as neurotransmitters. Many of the hypothalamic neuropeptides are synthesized as inactive precursors that are activated by proteolysis during axonal transport from the cell body to the synapse. Studies in which the paraventricular nuclei were bilaterally destroyed have shown that the neuroendocrine cells in the hypothalamus show functional plasticity and cells that do not usually make detectable quantities of a particular neuropeptide may be activated to do so. Within the hypothalamic nuclei are dense networks of synaptic connections among neurons synthesizing the same or different neuropeptides. These local circuits may coordinate the activities of peptidergic neurons in a hypothalamic nucleus. Hypothalamic neurons project axons to the median eminence-pituitary stalk and the posterior pituitary, also to nuclei within the hypothalamus and to extrahypothalamic areas such as the lower brainstem. Peptidergic neurons in the hypothalamus can have combined neurohormonal and neurotransmitter activities mediated by axon terminals on portal capillaries and other hypothalamic nuclei. Double labelling immunohistochemistry has been used to demonstrate reciprocal connections between peptidergic neurons in the hypothalamus, such as those synthesizing growth hormone-releasing hormone and somatostatin.

Animals↗
PubMed1991

An immunohistochemical study of the GnRH neuron morphology and topography in the adult female rabbit hypothalamus.

The morphology and distribution of immunoreactive (GnRH) neural elements in the hypothalamus of the adult nulliparous female rabbit were examined. Approximately 1,000 GnRH cells (range 890-1136) were counted in the right half of the hypothalamus. Two distinct GnRH cell types were observed: GnRH cells with rough or spiny contours accounted for 64% of the total immunoreactive cells, and smooth-contoured cells represented 34% of the total. The majority of immunoreactive neural elements were found in the anterior hypothalamus. GnRH cells and processes were located primarily in the ventral and medial anterior hypothalamus forming an inverted V pattern. Processes were followed from the medial preoptic area and suprachiasmatic nucleus to the infundibular stem. Extrahypothalamic projections of GnRH cells were observed. Immunoreactive fibers were also found to contact the ependymal lining of the third ventricle. It is concluded that two morphologically distinct GnRH cell types exist and have a broad distribution in the rabbit hypothalamus. The functional significance of these cell types requires further study.

Animals↗
PubMed2004

Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions.

In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin-releasing hormone (CRH)-producing neurons that control the hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the hypothalamus, of which more than 50% was active, that is, contained activated macrophages. MS patients have increased numbers of CRH-immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of chronic activation of CRH neurons and increased CRH mRNA expression. Active MS lesions correlated with a low number of hyperactive CRH/VP neurons. High human leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and microglial activation, correlated with low CRH mRNA expression. The nearer the HLA expression was situated to the CRH neurons, the stronger the inhibiting effect, suggesting that activated microglial cells or macrophages suppress these neurons. The more active MS lesions were present in the hypothalamus, the shorter was the disease duration until the moment of death, indicating an unfavorable course of the disease. Thus, MS patients have a chronically activated CRH system, but, in the subgroup of patients with active MS lesions in the hypothalamus, this activation is impaired and the disease course is worse.

Adult↗
PubMed2002

Distribution of vesicular glutamate transporter mRNA in rat hypothalamus.

Two isoforms of the vesicular glutamate transporter, VGLUT1 and VGLUT2, were recently cloned and biophysically characterized. Both VGLUT1 and VGLUT2 specifically transport glutamate into synaptic vesicles, making them definitive markers for neurons using glutamate as a neurotransmitter. The present study takes advantage of the specificity of the vesicular transporters to afford the first detailed map of putative glutamatergic neurons in the rat hypothalamus. In situ hybridization analysis was used to map hypothalamic distributions of VGLUT1 and VGLUT2 mRNAs. VGLUT2 is clearly the predominant vesicular transporter mRNA found in the hypothalamus; rich expression can be documented in regions regulating energy balance (ventromedial hypothalamus), neuroendocrine function (preoptic nuclei), autonomic tone (posterior hypothalamus), and behavioral/homeostatic integration (lateral hypothalamus, mammillary nuclei). Expression of VGLUT1 is decidedly more circumspect and is confined to relatively weak labeling in lateral hypothalamic regions, neuroendocrine nuclei, and the suprachiasmatic nucleus. Importantly, dual-label analysis revealed no incidence of colocalization of VGLUT1 or VGLUT2 mRNAs in glutamic acid decarboxylase (GAD) 65-positive neurons, indicating that GABA neurons do not express either transporter. Our data support a major role for hypothalamic glutamatergic neurons in regulation of all aspects of hypothalamic function.

Animals↗
PubMed2002

Endomorphin-1 and -2 immunoreactive cells in the hypothalamus are labeled by fluoro-gold injections to the ventral tegmental area.

Endomorphin-1 and -2 (EM1, EM2) are endogenous opioids with high affinity and selectivity for the mu-opioid receptor. Cells expressing EM-like immunoreactivity (EM-LI) are present in the hypothalamus, and fibers containing EM-LI project to many brain regions, including the ventral tegmental area (VTA). The VTA is one of the most sensitive brain regions for the rewarding and locomotor effects of opioids. It contains mu-opioid receptors, which are thought to mediate gamma-aminobutyric acid-dependent disinhibition of dopamine transmission to the nucleus accumbens. We investigated whether hypothalamic EM-LI cells project to the VTA, where they could play a natural role in this circuitry. The retrograde tracer Fluoro-Gold (FG) was microinjected into the anterior or posterior VTA in rats. Nine days later, colchicine was injected, and 24 hours later, the animals were perfused and processed for fluorescence immunocytochemistry. Numerous FG-labeled cells were detected in the hypothalamus. Both EM1-LI and EM2-LI cells were present in the periventricular nucleus, between the dorsomedial and ventromedial hypothalamus and between the ventromedial and arcuate nuclei. Subpopulations of EM1-LI and EM2-LI cells were labeled by FG. Injections of FG to the anterior and posterior VTA were both effective in producing double-labeled cells, and an anterior-posterior topographical organization between the VTA and hypothalamus was observed. The results support the idea that some endomorphin-containing neurons in the hypothalamus project to the VTA, where they may modulate reward and locomotor circuitry.

Animals↗
PubMed2001

Characterization of CART neurons in the rat and human hypothalamus.

Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary nucleus (PMV). Intracerebroventricular administration of recombinant CART peptide decreases food intake and CART mRNA levels in the Arc are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the PMV. In the current study, we used double label in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical identity of the hypothalamic CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also found that CART neurons in the parvicellular PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We also observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers in the human hypothalamus indicates that CART may also play a role in the regulation of energy homeostasis in humans.

Adult↗
PubMed2001

Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus.

The excitatory amino acid neurotransmitter glutamate participates in the control of most (and possibly all) neuroendocrine systems in the hypothalamus. This control is exerted by binding to two classes of membrane receptors, the ionotropic and metabotropic receptor families, which differ in their structure and mechanisms of signal transduction. To gain a better understanding about the precise sites of action of glutamate and the subunit compositions of the receptors involved in the glutamatergic neurotransmission in the hypothalamus and septum, in situ hybridization was used with 35S-labeled cRNA probes for the different ionotropic receptor subunits, including glutamate receptor subunits 1-4 (GluR1-GluR4), kainate-2, GluR5-GluR7, N-methyl-D-aspartate (NMDA) receptor 1 (NMDAR1), and NMDAR2A-NMDAR2D. The results showed that subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-preferring, kainate-preferring, and NMDA-preferring receptor subunits are distributed widely but heterogeneously and that the GluR1, GluR2, kainate-2, NMDAR1, NMDAR2A, and NMDAR2B subunits are the most abundant in the hypothalamus. Thus, GluR1 subunit mRNA was prominent in the lateral septum, preoptic area, mediobasal hypothalamus, and tuberomammillary nucleus, whereas kainate-2 subunit mRNA was abundant in the medial septum-diagonal band, median and anteroventral preoptic nuclei, and supraoptic nuclei as well as the magnocellular portion of the posterior paraventricular nucleus. Regions that contained the highest levels of NMDAR1 subunit mRNA included the septum, the median preoptic nucleus, the anteroventral periventricular nucleus, and the supraoptic and suprachiasmatic nuclei as well as the arcuate nucleus. Together, the extensive distribution of the different GluR subunit mRNAs strengthen the view that glutamate is a major excitatory neurotransmitter in the hypothalamus. The overlap in the distribution of the various subunit mRNAs suggests that many neurons can express GluR channels that belong to different families, which would allow a differential regulation of the target neurons by glutamate.

Animals↗
PubMed1978

Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons.

The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuroepithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at this site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.

Animals↗
PubMed1990

Neuronal connections between the cerebellar nuclei and hypothalamus in Macaca fascicularis: cerebello-visceral circuits.

The purpose of this study was to identify the basic pattern of interconnections between the cerebellar nuclei and hypothalamus in Macaca fascicularis. The distribution of retrogradely labeled cells and anterogradely filled cerebellofugal axons in the hypothalamus of M. fascicularis was investigated after pressure injections of a horseradish peroxidase mixture (HRP + WGA-HRP) in the cerebellar nuclei. Following injections in the lateral, anterior, and posterior interposed cerebellar nuclei retrogradely labeled cells were present in the following areas (greatest to least concentration): lateral and dorsal hypothalamic areas, dorsomedial nucleus, griseum periventriculare hypothalami, supramammillary and tuberomammillary nuclei, posterior hypothalamic area, ventromedial nucleus and periventricular hypothalamus, around the medial mammillary nucleus, lateral mammillary nucleus, and infundibular nucleus. Cell labeling was bilateral with an ipsilateral preponderance. In these same experiments anterogradely labeled cerebellar efferent fibers terminated in the contralateral posterior, dorsal and lateral hypothalamic areas, and the dorsomedial nucleus. In these regions retrogradely labeled hypothalamic cells were occasionally found in areas that also contained anterogradely filled cerebellar axons. This suggests a partial reciprocity in this system. In addition, sparse numbers of labeled cerebellar fibers recross in the hypothalamus to distribute to homologous areas ipsilateral to the injection site. Subsequent to an injection in the medial cerebellar nucleus (NM), cell labeling was present in more rostral hypothalamic levels including the lateral and dorsal hypothalamic areas, the dorsomedial nucleus, around or in fascicles of the column of the fornix, and in the periventricular hypothalamic area. Although no fastigiohypothalamic fibers were seen in this study, on the basis of information available from the literature it is likely that such a connection exists in primates. In summary, hypothalamic projections to NM originated mainly from rostral to midhypothalamic levels, whereas those projections to the lateral three cerebellar nuclei came from mid and more caudal levels. The existence of direct hypothalamic projections to cerebellar nuclei in M. fascicularis and of cerebellofugal projection to some hypothalamic centers indicates that circuitry is present through which the cerebellum may influence visceral functions. Furthermore, the fact that projections to NM versus the other cerebellar nuclei originate from somewhat different regions of the hypothalamus would suggest that the visceral functions modulated by each pathway is not the same.

Animals↗
PubMed1990

GABA: a dominant neurotransmitter in the hypothalamus.

To study the organization and distribution of the inhibitory amino acid neurotransmitter GABA in the medial hypothalamus, we used a postembedding immunocytochemical approach with colloidal gold. Quantitative analysis showed that half (49%) of all synapsing boutons studied were immunoreactive for GABA, based on immunogold staining of the suprachiasmatic, arcuate, supraoptic, and paraventricular nuclei. This was corroborated with pre-embedding peroxidase immunostaining with antisera against glutamate decarboxylase, the GABA synthetic enzyme. These data suggest that GABA is the numerically dominant neurotransmitter in the hypothalamus, and emphasize the importance of inhibitory circuits in the hypothalamus. Serial ultrathin sections were used to reconstruct GABA immunoreactive boutons and axons in three dimensions. With this type of analysis we found less morphological heterogeneity between GABA immunoreactive boutons than with single ultrathin sections. Single sections sometimes showed boutons containing only small clear vesicles, and other with both clear vesicles and small dense core vesicles. However, with serial sections through individual boutons, dense core vesicles were consistently found at the periphery of the pre-synaptic GABA immunoreactive boutons, suggesting probable co-localization of GABA with unidentified peptides in most if not all boutons throughout the hypothalamus. A positive correlation was found between the density of small clear vesicles and the intensity of immunostaining with colloidal gold particles. GABA immunoreactive axons generally made symmetrical type synaptic specializations, although a small percentage made strongly asymmetrical synaptic specializations. Vesicles in GABA immunoreactive boutons were slightly smaller than those in non-reactive boutons. Synaptic efficacy is related to the position of the synapse on the post-synaptic neuron. While the majority of GABA immunoreactive axons made synaptic contact with dendrites, the distribution of GABA immunoreactive synapses on somata and dendrites was the same as would be expected from a random distribution of all boutons. No preferential innervation of cell bodies by GABA immunoreactive terminals was found. Serial ultrathin sections showed that a GABA immunoreactive axon would sometimes make repeated synaptic contacts with a single postsynaptic neuron, indicating a high degree of direct control by the presynaptic GABAergic cell. Other immunoreactive axons made synaptic contact with a number of adjacent dendrites and cells, suggesting a role for GABA in synchronizing the activity of hypothalamic neurons. Based on the density of immunogold particles per unit area, varying concentrations of immunoreactive GABA were found in different presynaptic boutons in the hypothalamus.

Animals↗
PubMed1991

Alz-50 immunoreactivity in the hypothalamus of the normal and Alzheimer human and the rat.

Alz-50 is a monoclonal antibody recognizing a 68 kilodalton protein that is abundant in Alzheimer's disease (AD) but not detectable by immunoblotting methods in normal brains. When used for immunohistochemistry in AD cortex, Alz-50 recognizes large numbers of neurofibrillary tangles (NFT), neuritic plaques, and some neurons that show no evidence of neurofibrillary degeneration by conventional histopathological staining methods. Alz-50 immunoreactivity is described at the light and electron microscopic levels in the hypothalamus of brains obtained at autopsy from normal and AD subjects. Alz-50 immunoreactivity in the rat hypothalamus is also described. A well-defined population of Alz-50 immunoreactive hypothalamic neurons was identified in both the normal human and rat. At the light microscopic level in the normal human, immunoreactive neurons were most concentrated in the periventricular region, but were also scattered throughout the arcuate nucleus (ARC), lateral hypothalamic area, and tuberal region. Immunoreactive fibers were seen in the periventricular region, dorsal division of the ventromedial nucleus (VMNd), ARC, and external layer of the median eminence (ME). In the rat, reactive neurons were seen only in the periventricular region, and reactive fibers were seen in the periventricular zone, medial preoptic nuclear complex, suprachiasmatic nucleus, VMNd, ARC, and external layer of the ME. Ultrastructurally, all immunoreactivity in the normal human and rat hypothalamus was associated with intraneuronal vesicles. In the AD hypothalamus, Alz-50 identified numerous senile plaques and NFT in addition to the cells and fibers that were stained in the normal brains. Immunoreactive plaques and NFT were most numerous in regions previously reported to undergo neurofibrillary degeneration. At the ultrastructural level, the immunoreactivity in the AD hypothalamus was associated with filaments as well as vesicles. The significance of the selective staining of a specific population of vesicles by Alz-50 is unknown; however, the present results suggest that it is independent of AD pathology.

Aged↗
PubMed1993

Localisation of mRNA encoding the protein precursor of galanin in the monkey hypothalamus and basal forebrain.

The hypothalamic and basal forebrain sites of synthesis of preprogalanin mRNA were identified in three adult monkeys (Macaca fascicularis) by in situ hybridisation performed with a radiolabelled cRNA probe transcribed from human preprogalanin cDNA. With stringent hybridisation conditions, the cRNA probe was hybridised to free-floating sections containing structures contiguous with the rostral hypothalamus through to the caudal limit of the hypothalamus as defined by the mammillary bodies. Specific hybridisation of the preprogalanin cRNA probe occurred throughout the hypothalamus but was particularly intense in the arcuate, paraventricular (parvicellular and magnocellular portions), and dorsomedial nuclei. Moderate hybridisation was found in the periventricular nucleus and scattered hybridisation in the medial preoptic nucleus. The medial preoptic area and the anterior and lateral hypothalamic areas showed moderate to intense hybridisation in scattered cells. A few cells in the tuberal portion and dorsal cap of the anterior portion of the supraoptic nucleus were labelled. Isolated cells were also labelled in the zona incerta. There was little labelling in the dorsal hypothalamic area but moderate labelling in the posterior hypothalamic area. Structures contiguous with the rostral hypothalamus including the diagonal band of Broca, bed nucleus of stria terminalis, substantia innominata, and basal nucleus of Meynert showed intense hybridisation. These data indicate a widespread distribution of preprogalanin mRNA in the monkey hypothalamus. A comparison with the previously reported distribution of preprogalanin mRNA in the rat, as well as with the distribution of galanin-like immunoreactivity in the rat and human, suggests some important species differences. Of particular interest were differences in the supraoptic, suprachiasmatic, and dorsomedial nuclei. The intense hybridisation throughout the paraventricular nucleus and in the rostral arcuate nucleus suggests that galanin may play a role in the regulation of both posterior and anterior pituitary function.

Animals↗
PubMed1993

Vasopressin and oxytocin gene expression in the human hypothalamus.

We studied the distribution of messenger ribonucleic acids coding for vasopressin and oxytocin in the human hypothalamus by means of hybridization histochemistry. Numerous large and medium-sized neurons contain vasopressin messenger ribonucleic acid in the paraventricular nucleus, supraoptic nucleus, and accessory magnocellular nucleus. Small, lightly labeled vasopressin neurons also were detected in the suprachiasmatic nucleus. In addition, a relatively sparse band of mostly ovoid, medium-sized vasopressin neurons mingle with unlabeled neurons of the lateral hypothalamic area; these cells extend dorsoventrally from the region ventral to the stria terminalis to the ventrolateral hypothalamus, sometimes transgressing the boundaries of nearby nuclei. We did not detect vasopressin gene expression in neurons of the bed nucleus of the stria terminalis proper, although some of the dorsal-most labeled neurons of the lateral hypothalamus extend into the region of the caudal bed nucleus. Some lateral hypothalamic neurons also encroach upon other extrahypothalamic structures, such as the zona incerta. The nucleus basalis of Meynert complex was, with only rare exceptions, devoid of cells containing vasopressin messenger ribonucleic acid. Oxytocin messenger ribonucleic acid is found in the supraoptic nucleus, paraventricular nucleus, accessory magnocellular nucleus and, less frequently, in neurons of the lateral hypothalamus. In the hypothalamic magnocellular nuclei, oxytocin neurons are somewhat smaller than vasopressin neurons. Vasopressin cells outnumber oxytocin cells in the supraoptic nucleus, but their numbers are comparable in the paraventricular nucleus. As with vasopressin neurons, lateral hypothalamic oxytocin cells loosely span several diencephalic nuclei and encroach occasionally upon adjacent regions. These results confirm that the organization of vasopressin and oxytocin neurons in the human hypothalamus is largely comparable to that in nonhuman species and demonstrate the utility of hybridization histochemistry for elucidating the chemoarchitecture of the human brain.

Adolescent↗
PubMed1994

Metabotropic glutamate receptor mGluR1 distribution and ultrastructural localization in hypothalamus.

The metabotropic glutamate receptor mGluR1 is a G-protein-coupled glutamate receptor whose activation induces phosphotidylinositol hydrolysis and increases diacylglycerol and cytoplasmic calcium. By using affinity-purified antisera against a partial amino acid sequence of mGluR1 alpha, deduced from the nucleotide sequence of the cloned gene, the heterogeneous expression of this glutamate receptor was studied immunocytochemically with light and electron microscopy in the rat hypothalamus. Immunoreactivity was restricted to cell bodies and dendrites throughout many regions of the adult hypothalamus, including the preoptic area, anterior hypothalamus, suprachiasmatic nucleus, dorsomedial hypothalamus, and periventricular region. Strong immunolabeling was found in the lateral hypothalamus where immunoreactivity could be detected as early as embryonic day 18. Intense immunoreactivity was also found in the medial mammillary nuclei. In contrast to the strong labeling in many other regions, the neuroendocrine neurons of the arcuate, supraoptic, and paraventricular nuclei showed relatively little staining in adults. With light microscopy, immunoperoxidase labeling was found distributed in patches on the cytoplasmic side of the plasma membrane of immunoreactive neurons. When the same tissue was examined ultrastructurally, the patches were not restricted to synaptic specializations but were also found distributed on perikaryal and dendritic membranes sometimes associated with synapses and sometimes not. Some immunoreactive membranes showed no immunolabeling at the synaptic junction. When the tissue was strongly stained, labeling could be found in the cytoplasm of immunoreactive cells. No immunostaining was found on axons or presynaptic boutons. Together with other evidence showing a widespread expression of many different subtypes of both ionotropic and metabotropic receptors, these data support the hypothesis that glutamate may regulate hypothalamic cellular activity with a number of physiologically different mechanisms, and these mechanisms include second-messenger systems activated by G proteins.

Aging↗
PubMed1995

Non-NMDA glutamate receptors are present throughout the primate hypothalamus.

To determine the distributions of glutamate receptors throughout the macaque hypothalamus, we utilized highly specific antipeptide antibodies to visualize alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunits (GluR1, GluR2 and GluR3 [designated as GluR2/3], and GluR4); kainate receptor subunits (GluR6 and GluR7, [designated as GluR6/7]), and a metabotropic receptor (mGluR1 alpha). The results indicate that these glutamate receptors are distributed differentially throughout the monkey hypothalamus. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors are the dominant non-N-methyl-D-aspartate glutamate receptors within the monkey hypothalamus, and the GluR2 subunit is most abundant. GluR1-immunoreactive neurons and neuropil are observed predominantly in the tuberal and mammillary nuclei. GluR2/3-immunoreactive neurons and neuropil have a broader distribution within preoptic, anterior, tuberal, and caudal regions. Separate (but partially overlapping) distributions of GluR1- and GluR2/3-immunoreactive neurons were found, suggesting that the GluR1, GluR2, and/or GluR3 subunits may be coexpressed in subsets of hypothalamic neurons. In contrast, GluR4 immunoreactivity was expressed minimally within monkey hypothalamus. GluR6/7 immunoreactivity was enriched selectively within the suprachiasmatic nucleus. mGluR1 alpha immunoreactivity was present in the mammillary complex. The localization of non-N-methyl-D-aspartate glutamate receptor subunits to neurons throughout the macaque hypothalamus provides further evidence for the glutamatergic regulation of neuroendocrine, autonomic, and limbic circuits. Differential distributions of glutamate receptor subunits may increase the dynamic range of the effects of presynaptic glutamate, allowing for the regulation of several distinct functions subserved by hypothalamic neurons.

Amino Acid Sequence↗
PubMed1975

A fluorescence microscopic study of the distribution of monoamines in the hypothalamus of the cat.

Three distinct groups of monoamine (MA)-containing nerve cell bodies have been visualized in the hypothalamus and preoptic area of the cat by means of the Falck-Hillarp fluorescence histochemical technique. First, numerous small-sized catecholamine (CA) type neurons were disclosed within the ventral half of the periventricular area in the supraoptic and middle hypothalamic regions. The round to oval neurons of this medio-ventral group were more especially abundant around the base of the third ventricle, within the arcuate and supraopticus diffusus nuclei. Numerous medium-sized CA perikarya identified as the dorsal group, were also mapped out in the dorsal and posterior hypothalamic areas. Finally, a small population of both CA and serotonin (5-hydroxytryptamine, 5-HT)-containing neurons was disclosed within the lateral area of the middle and mammillary hypothalamic regions. These multipolar or elongated neurons which compose the lateral group were lying either along the ventrolateral surface of the hypothalamus or around the ventrolateral aspect of the fornix. In addition to these three MA cell groups, a few cells displaying a fluorescence of the CA type were also visualized in the so-called "dorsal chiasmatic nucleus" after alpha-methyl-dopa treatment. High density of CA axon terminals were found, on the other hand, in the extrenal layer of the median eminence, in the dorsomedial, paraventricular supraoptic and suprachiasmatic nuclei, and also within nucleus interstitialis of stria terminalis. In the present study, however, it was possible to identify with certainty any concentration of 5-HT axon terminals in the cat hypothalamus. Therefore, except for the lateral cell group which could be peculiar to the cat, the topographical distribution of MA nerve cell bodies and axon terminals in the hypothalamus of the cat appears similar to the morphological organization of the MA neuronal elements in the hypothalamus of the rat.

Animals↗