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Importance of endogenous nitric oxide synthase in the rat hypothalamus and amygdala in mediating the response to capsaicin.

Although capsaicin has been shown to activate certain neuronal groups in the hypothalamus and amygdala, the neurotransmitters involved and the exact mechanism of action are not clearly understood at present. The aim of this study was to examine the hypothesis that the effect of capsaicin in the rat hypothalamus and amygdala primarily involves direct activation of the endogenous nitric oxide synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO). Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a significant increase in Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and medial and cortical amygdala. The expression of nicotinamide adenine dinucleotide phosphate diaphorase, a histochemical marker for NOS, was also increased in these brain areas in addition to the periventricular and lateral hypothalamic area and central amygdaloid nucleus. Also, capsaicin significantly increased the expression of neuronal NOS messenger RNA and protein in the PVN, SON, and medial amygdala as demonstrated by in situ hybridization and immunohistochemistry, respectively. A higher proportion of the NOS neurons in the PVN, periventricular region, SON and amygdala showed Fos expression in response to capsaicin than vehicle injection. There was little, if any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area. The capsaicin-induced activation of the hypothalamic PVN and SON neurons and the medial amygdaloid nucleus was attenuated in the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) -pretreated animals in comparison with the inactive enantiomer D-NAME. These observations indicate that activation of the endogenous NOS system and production of NO constitute a major pathway through which capsaicin exerts its effect within the hypothalamus and amygdala.

Amygdala↗

5-Methoxytryptamine in rat hypothalamus and human CSF. A fact or artifact?

Using thin-layer chromatography fluorometry, gas chromatography mass spectrometry and field ionization mass spectrometry the findings of Green et al. regarding the identification of 5-methoxytryptamine in rat hypothalamus could not be confirmed. On derivatization using pentafluoropropionic anhydride, melatonin underwent partial transacylation to yield 5-methoxytryptamine as one of the by-products. We thus consider the finding of 5-methoxytryptamine in rat hypothalamus by mass fragmentography as an artifact forming from melatonin, which is normally present in rat hypothalamus.

5-Methoxytryptamine↗

Organization of human hypothalamus in fetal development.

The organization of the human hypothalamus was studied in 33 brains aged from 9 weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin, calbindin, calretinin, neuropeptide Y, neurophysin, growth-associated protein (GAP)-43, synaptophysin, and the glycoconjugate 3-fucosyl- N-acetyl-lactosamine. Developmental stages are described in relation to obstetric trimesters. The first trimester (morphogenetic periods 9-10 w.g. and 11-14 w.g.) is characterized by differentiating structures of the lateral hypothalamic zone, which give rise to the lateral hypothalamus (LH) and posterior hypothalamus. The PeF differentiates at 18 w.g. from LH neurons, which remain anchored in the perifornical position, whereas most of the LH cells are displaced laterally. A transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus differentiated at 13-16 w.g., three principal parts, the ventrolateral part, the dorsomedial part, and the shell, were revealed by distribution of calbindin, calretinin, and GAP43 immunoreactivity. The second trimester (morphogenetic periods 15-17 w.g., 18-23 w.g., and 24-33 w.g.) is characterized by differentiation of the hypothalamic core, in which calbindin- positive neurons revealed the medial preoptic nucleus at 16 w.g. abutted laterally by the intermediate nucleus. The dorsomedial nucleus was clearly defined at 10 w.g. and consisted of compact and diffuse parts, an organization that was lost after 15 w.g. Differentiation of the medial mamillary body into lateral and medial was seen at 13-16 w.g. Late second trimester was marked by differentiation of periventricular zone structures, including suprachiasmatic, arcuate, and paraventricular nuclei. The subnuclear differentiation of these nuclei extends into the third trimester. The use of chemoarchitecture in the human fetus permitted the identification of interspecies nuclei homologies, which otherwise remain concealed in the cytoarchitecture.

Biomarkers↗

Corticotropin-releasing hormone-synthesizing neurons of the human hypothalamus receive neuropeptide Y-immunoreactive innervation from neurons residing primarily outside the infundibular nucleus.

Immunohistochemical single- and double-labeling studies were performed on the hypothalami of postmortem human brains to elucidate the distribution of corticotropin-releasing hormone (CRH)-immunoreactive (IR) neuronal elements and their interaction with the neuropeptide Y (NPY)-ergic neuronal system. The great majority of CRH-IR perikarya were found in the paraventricular nucleus (PVN), whereas a considerable number of CRH-IR neurons were also observed in the periventricular and infundibular nuclei. The dorsomedial nucleus and the perifornical region contained only scattered CRH-IR neurons. Dense CRH-IR fiber networks were found throughout the hypothalamus. However, the medial preoptic, the dorsolateral part of the supraoptic, the suprachiasmatic, the ventromedial, and the different mammillary nuclei showed a relative paucity of fibers. The terminal fields of NPY-IR axons overlapped the distribution of CRH-IR neurons in the hypothalamus. NPY-IR axon varicosities were juxtaposed to both dendrites and perikarya of the majority of CRH-IR neurons residing in the paraventricular, periventricular, and infundibular nuclei. These neurons were frequently contacted by multiple NPY axons that either formed baskets around their perikarya or completely ensheathed the emanating CRH dendrites. Because NPY and agouti-related protein (AGRP) are co-contained in neurons of the human infundibular nucleus, we used AGRP as a marker of NPY fibers originating exclusively from the infundibular nucleus. Only a small proportion of CRH neurons in the PVN was contacted by AGRP-IR axon varicosities, suggesting that NPY-IR innervation of CRH neurons in the PVN derive mainly from regions outside the infundibular nucleus. The present morphological findings support the view that NPY regulates the CRH system of the human hypothalamus and therefore at least some of the effects of NPY on metabolic, autonomic, and endocrine functions may be mediated through CRH.

Adult↗

Distribution of the neuropeptide FF1 receptor (hFF1) in the human hypothalamus and surrounding basal forebrain structures: immunohistochemical study.

Neuropeptides with C-terminal RFamide and their receptors NPFF1 (FF1) and NPFF2 (FF2) have been implicated in a wide variety of functions, including nociception and autonomic and neuroendocrine regulation. Recent studies indicate that the FF1, but not FF2, mRNA is highly expressed in the human hypothalamus. In the present study, localization of FF1 in the human hypothalamus and surrounding regions was studied immunohistochemically by using an antibody against human FF1 (hFF1). Brain sections from healthy 30-50-year-old individuals were used for hFF1 immunohistochemistry. The highest density of hFF1-stained cells was found in the posterior division of the bed nucleus of the stria terminalis and in the zona incerta. A moderate density of cells was observed in the perifornical nucleus, infundibular nucleus, tuberomammillary nucleus, and lateral tuberal nucleus. A lesser density was revealed in the dorsomedial hypothalamic nucleus, basal nucleus of Meynert, and anterior amygdaloid area. Only scattered hFF1 cells were found in the suprachiasmatic nucleus and hypothalamic paraventricular nucleus. hFF1 cells and fibers were absent in the supraoptic and mammillary nuclei. Single and double strands of hFF1-immunopositive punctate varicosities marked cellular processes of different caliber. The density of hFF1-immunostained fiber networks did not always coincide with that of hFF1-immunostained cells. hFF1 immunoreactivity was also found in the wall of blood vessels within most brain areas studied. Localization of hFF1 in discrete regions of the hypothalamus and extended amygdala may provide important insights into the role of amidated neuropeptides in central autonomic and neuroendocrine control in the human brain.

Adult↗

Coexpression of dynorphin and neurokinin B immunoreactivity in the rat hypothalamus: Morphologic evidence of interrelated function within the arcuate nucleus.

Considerable evidence suggests that dynorphin and neurokinin B (NKB) neurons in the hypothalamic arcuate nucleus participate in the sex-steroid regulation of reproduction. In the present study, we used dual-label immunofluorescence to explore the distribution of prodynorphin and proNKB immunoreactivity in the rat hypothalamus. Additionally, we investigated whether arcuate prodynorphin-ir (immunoreactive) neurons expressed the neurokinin 3 receptor (NK3R) or nuclear estrogen receptor-alpha (ERalpha). We found that the majority of prodynorphin-ir neurons in the rat arcuate nucleus expressed proNKB, whereas nearly all (99%) of the proNKB neurons were immunoreactive for prodynorphin. The arcuate nucleus was the only site in the hypothalamus where neuronal somata coexpressing prodynorphin and proNKB-immunoreactivity were identified. A dense plexus of double-labeled prodynorphin/proNKB-ir fibers was found within the arcuate nucleus extending to the median eminence and throughout the periventricular zone of the hypothalamus. Prodynorphin/proNKB fibers were also identified in the paraventricular nucleus, anterior hypothalamic area, medial preoptic area, median preoptic nucleus, anteroventral periventricular nucleus, and bed nucleus of the stria terminalis in a distribution consistent with previously described arcuate nucleus projections. Interestingly, the majority of prodynorphin-ir neurons in the arcuate nucleus expressed NK3R, and nearly 100% of the prodynorphin-ir neurons contained nuclear ERalpha. Our results suggest that there is a close functional relationship between dynorphin and NKB peptides within the arcuate nucleus of the rat, which may include an autofeedback loop mediated through NK3R. The diverse hypothalamic projections of fibers expressing both prodynorphin and proNKB provide evidence that these neurons may participate in a variety of homeostatic and neuroendocrine processes.

Animals↗

The efferent connections of the suprachiasmatic nucleus of the hypothalamus.

The efferent connections of the suprachiasmatic nucleus of the hypothalamus have been studied in the rat by the injection of 3H-proline into the nucleus and the surrounding regions of the rostral hypothalamus, and by the injection of the enzyme marker, horseradish peroxidase, into the region of the ventromedial hypothalamic nucleus. After an injection of 3H-proline confined to the ventral portion of the suprachiasmatic nucleus, transported label can be followed, in the autoradiographs, dorsally and caudally in the periventricular area as far as the caudal end of the ventromedial nucleus, into the triangular area between this nucleus and the arcuate nucleus, and along the ventral aspect of the tuberal region, just lateral to the ventromedial nucleus. A small number of silver grains are also seen over the internal lamina of the median eminence. No label can be followed rostrally or immediately lateral to the nucleus. Comparable injections into adjoining regions of the hypothalamus (especially the anterior hypothalamic area, the medial preoptic area, and the retrochiasmatic region) show transported label over the same regions, but with a somewhat different pattern of grain distribution; in addition, the anterior hypothalamic area shows an extensive projection through the medial forebrain bundle to the mammillary and supramammillary nuclei, the midbrain tegmentum, and certain of the midline thalamic nuclei. Although it is difficult in our autoradiographs to distinguish between the course of the efferent fibers from the suprachiasmatic nucleus and the zones in which they terminate, our evidence favors a termination among the cells of the periventricular area, and upon dendrites of the cells in the ventromedial, dorsomedial and arcuate nuclei, which extend beyond the limits of the nuclei into the periventricular area and to the area beneath the ventromedial nucleus.

Amygdala↗

Localization of tyrosine hydroxylase-immunoreactive neurons in the cat hypothalamus, with special reference to fluorescence histochemistry.

The present study examines the distribution and morphological characteristics of neurons containing immunoreactivity of tyrosine hydroxylase in the cat hypothalamus. We used the indirect immunoperoxidase technique on vibratome sections. Tyrosine hydroxylase-immunoreactive cell bodies were widely distributed in discrete regions of the cat hypothalamus. Several principal cell groups were identified. They were seen in the posterior and dorsal hypothalamic areas, zona incerta, dorsomedial and lateral hypothalamic areas, arcuate nucleus, periventricular nucleus, paraventricular nucleus, and an area of the tuber cinereum and preoptic area. These cells presented two different morphological characteristics; small with two to three short processes and medium to large, multipolar with three to five long dendritic trees. The atlas is presented in twelve cross-sectional drawings of the cat hypothalamus from the level A8.5 to A15 of the Horsley-Clarke stereotaxic planes. We also examined the distribution of hypothalamic catecholamine fluorescent neurons by using the aqueous aldehyde method in combination with glyoxylic acid applied to vibratome sectioned tissues, which improves sensitivity. Comments are made on the relative localizations of the tyrosine hydroxylase-immunoreactive and aldehyde-induced histofluorescent cells, as well as on species differences between the cat, rat, and mouse.

Animals↗

Immunocytochemical demonstration of dynorphin(PH-8P)-like immunoreactive elements in the human hypothalamus.

PH-8P (dynorphin[1-8])-like immunoreactive neuronal perikarya, processes, and terminals located within the human hypothalamus were investigated by the avidin-biotin peroxidase complex (ABC) immunocytochemical procedure. Immunopositive neurons were distributed throughout the hypothalamus. The distributional pattern was found to be similar to that in other mammalian species by the use of antisera against dynorphin. A large number of immunoreactive neuronal perikarya were detected in the supraoptic nucleus (SON) and the magnocellular portion of the paraventricular nucleus (PVN). Their processes appeared to project to the posterior pituitary via the internal layer of the median eminence and their distribution seemed to be less dense than in other mammalian species. PH-8P and vasopressin were colocalized in the neuronal perikarya in the human SON unlike the colocalization of these peptides in the rat SON and PVN. There were a few immunoreactive terminals in the external layer of the median eminence; their immunoreactive substances may be released into the portal veins to act on anterior pituitary cells. In addition, PH-8P-like immunoreactive neurons in the human hypothalamus may project to the extrahypothalamic area.

Dynorphins↗

The visually related posterior pretectal nucleus in the non-percomorph teleost Osteoglossum bicirrhosum projects to the hypothalamus: a DiI study.

This study was done to elucidate the ancestral (plesiomorphic) condition for visual pathways to the hypothalamus in teleost fishes. Three patterns of pretectal organization can be discerned morphologically and histochemically in teleosts. Their taxonomic distribution suggests that the intermediately complex pattern (seen in most teleost groups) is ancestral to both the elaborate pattern (seen in percomorphs) and the simple pattern (seen in cyprinids). The pretectal nuclei involved can be demonstrated with acetylcholinesterase histochemistry selectively and reliably in different species of teleosts, suggesting that the same-named nuclei are homologous in representatives of the three different patterns. Whereas there are visual pathways to the hypothalamus in both the elaborate (percomorph) and the simple (cyprinid) patterns, different pretectal and hypothalamic nuclei are involved. Thus visual hypothalamic pathways in these two patterns would not appear to be homologous. In this study, circuitry within the third, i.e., the intermediately complex, pattern is investigated. It is demonstrated that visual pathways project via the pretectum to the hypothalamus in Osteoglossum bicirrhosum and that they are very similar to the visual pathways in the elaborate pattern. This suggests that the circuitry in the intermediately complex pattern, as represented by Osteoglossum, is plesiomorphic (evolutionarily primitive) and the circuitry in both the simple pattern (seen in cyprinids) and the elaborate pattern (seen in percomorphs) is apomorphic (evolutionarily derived) for teleosts.

Animals↗

Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat.

The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis (BST), and rostral hypothalamus. In the present study we re-examined the projection of the ventral subiculum to these regions with the Phaseolus vulgaris leucoagglutinin (PHAL) method in the rat. The results confirm and extend earlier conclusions based primarily on the autoradiographic method. Projections from the ventral subiculum course either obliquely through the angular bundle to innervate the amygdala and adjacent parts of the temporal lobe, or follow the alveus and fimbria to the precommissural fornix and medial corticohypothalamic tract. The major amygdalar terminal field is centered in the posterior basomedial nucleus, while other structures that appear to be innervated include the piriformamygdaloid area, the posterior basolateral, posterior cortical, posterior, central, medial, and intercalated nuclei, and the nucleus of the lateral olfactory tract. Projections from the ventral subiculum reach the BST mainly by way of the precommissural fornix, and provide rather dense inputs to the anterodorsal area as well as the transverse and interfascicular nuclei. The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, "shell" of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary nucleus. We also observed a rather dense terminal field just dorsal to the suprachiasmatic nucleus that extends dorsally and caudally to fill the subparaventricular zone along the medial border of the anterior hypothalamic nucleus and ventrolateral border of the paraventricular nucleus. The general pattern of outputs to the hypothalamus and septum is strikingly similar for the ventral subiculum and suprachiasmatic nucleus, the endogenous circadian rhythm generator.

Amygdala↗

Beacon immunoreactivity in the rat hypothalamus.

Beacon (BC) is a peptide of 73 amino acids, whose gene expression was first reported in the hypothalamus of Psammomys obesus (or Israeli sand rat). To appreciate better the functional role of BC in normal rats and sand rats, the distribution of BC immunoreactivity (irBC) and its subcellular localization were studied in the brain of Sprague-Dawley rats. In the hypothalamus, intense staining was present in neurons of the supraoptic (SO), paraventricular (PVH), and accessory neurosecretory nuclei and in cell processes of median eminence. Double labeling of the hypothalamic sections with mouse monoclonal oxytocin (OT) antibody and rabbit polyclonal BC antiserum revealed that nearly all OT-immunoreactive cells from SO, PVH, and accessory neurosecretory nuclei were irBC. Double labeling of the sections with guinea pig vasopressin (VP) antiserum and BC antiserum showed that a population of VP-immunoreactive neurons was irBC. By immunoelectron microscopy, immunoreactive product was associated with mitochondrial membranes or appeared as electron-dense bodies in many PVH and SO neurons. Most of the neurosecretory granules were unstained for BC. Taken together, our results indicate the presence of beacon in the OT-containing neurons and a population of VP-containing neurons, mostly associated with mitochondrial membrane. Insofar as the amino acids sequence of beacon is identical to that of ubiquitin-like 5, it is possible that the distribution of BC immunoreactivity noted in our study is that of ubiquitin-like 5 peptide in the rat hypothalamus.

Animals↗

Evidence for an absence of estrogen-concentration by CCK-immunoreactive neurons in the hypothalamus of the female rat.

It is becoming increasingly clear that the neuropeptide cholecystokinin (CCK), widely distributed in the rat hypothalamus and limbic system, is subject to both organizational and activational influences of steroid hormones. Sex differences in numbers of CCK-immunoreactive elements have been demonstrated in sexually dimorphic structures such as the bed nucleus of the stria terminalis, medial preoptic nucleus, and ventromedial nucleus of the hypothalamus. Steroid activation of CCK has been indicated by findings that hypothalamic CCK levels and binding capacity vary over the estrous cycle. These studies, in combination with evidence of CCK mediation of sexually differentiated functions, prompted us to test for estrogen concentration among CCK-containing cells of the female rat hypothalamus by combining the techniques of immunohistochemistry and autoradiography. A method employing 2-week ovariectomies and perfusion fixation with 4% paraformaldehyde was compatible with the localization of both estrogen-accumulating and CCK-immunoreactive cell bodies. The maintenance of numbers of CCK-positive cells after gonadectomy suggested that expression of this peptide may not be directly regulated by ovarian steroids in female rats. This suggestion was substantiated by the finding that, with rare exceptions, CCK-immunoreactive cells did not concentrate estrogen in tissues collected from the anterior-posterior extent of the bed nucleus of the stria terminalis, medial preoptic nucleus, anterior hypothalamic area, and paraventricular nucleus.

Animals↗

5-HT3 receptors which modulate [3H]5-HT release in the guinea pig hypothalamus are not autoreceptors.

The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the electrically evoked release of [3H]5-HT from preloaded slices of the guinea pig brain. In the present study, 2-methyl-5-HT (1 microM) was also found to increase the K+ evoked release of [3H]5-HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5-HT3 antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K(+)-evoked release of [3H]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus suggesting that the 5-HT3 receptors mediating this effect are not located directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter the K(+)-evoked release of [3H]5-HT in a synaptosomal preparation of the same brain structure, even at a concentration 10-fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5-HT3 receptors are not located on 5-HT terminals in the guinea pig hypothalamus and therefore are not autoreceptors.

Animals↗

Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus.

The aim of this study was to determine the effects of leptin treatment on prepro-orexin and orexin receptor expression in the rat hypothalamus. Adult male rats, food-deprived for 48 and 72 h, were treated one time with vehicle or leptin (10 microg, icv). Prepro-orexin mRNA content was measured by semiquantitative RT-PCR, Northern blot, and in situ hybridization; orexin receptor 1 and 2 mRNA content was quantified by Northern blot and/or semiquantitative RT-PCR. Our results indicate that leptin inhibits a fasting-induced increase in prepro-orexin mRNA and orexin receptor 1 mRNA levels in the rat hypothalamus, while orexin receptor 2 mRNA levels were unchanged in all situations evaluated. These data provide direct evidence for an additional mechanism of adaptation of the hypothalamus to food deprivation and for a new effect of leptin in the regulation of food intake.

Animals↗

Dose-dependent effects of central leptin gene therapy on genes that regulate body weight and appetite in the hypothalamus.

We have examined the dose-dependent effects and central action of intraventricular administration of a recombinant adeno-associated virus encoding rat leptin (rAAV-leptin) in suppressing body weight (BW) gain in adult female rats. A low dose of rAAV-leptin (5x10(10) particles) suppressed weight gain (15%) without changing daily food intake (FI), but a twofold higher dose decreased BW by 30% along with a reduction in daily FI. Reduced BW was due to a loss in body adiposity because serum leptin was reduced. Serum insulin levels were decreased (96%) by only the high dose along with a slight reduction in glucose. Uncoupling protein-1 (UCP-1) mRNA expression in brown adipose tissue (BAT), reflecting energy expenditure through thermogenesis, was upregulated to the same magnitude by the two rAAV-leptin doses. We analyzed by in situ hybridization the expression in the hypothalamus of genes encoding the appetite-regulating neuropeptides. Only the high dose decreased expression of neuropeptide Y (NPY), the orexigenic peptide, and increased proopiomelanocortin (POMC), precursor of the an orexigenic peptide, alpha-MSH. Our studies show for the first time that increased availability of leptin within the hypothalamus through central leptin gene therapy dose-dependently decreases weight gain, adiposity, and serum insulin by increasing energy expenditure and decreasing FI. The decrease in FI occurs only when NPY is reduced and alpha-MSH is increased in the hypothalamus by the high dose of rAAV-leptin. Delivery of the leptin gene centrally through rAAV vectors is a viable therapeutic modality for long-term control of weight and metabolic hormones.

Agouti-Related Protein↗

Sexual differentiation of the human hypothalamus.

Functional sex differences in reproduction, gender and sexual orientation and in the incidence of neurological and psychiatric diseases are presumed to be based on structural and functional differences in the hypothalamus and other limbic structures. Factors influencing gender, i.e., the feeling to be male or female, are prenatal hormones and compounds that change the levels of these hormones, such as anticonvulsants, while the influence of postnatal social factors is controversial. Genetic factors and prenatal hormone levels are factors in the determination of sexual orientation, i.e. heterosexuality, bisexuality or homosexuality. There is no convincing evidence for postnatal social factors involved in the determination of sexual orientation. The period of overt sexual differentiation of the human hypothalamus occurs between approximately four years of age and adulthood, thus much later than is generally presumed, although the late sexual differentiation may of course be based upon processes that have already been programmed in mid-pregnancy or during the neonatal period. The recently reported differences in a number of structures in the human hypothalamus and adjacent structures depend strongly on age. Replication of these data is certainly necessary. Since the size of brain structures may be influenced by premortem factors (e.g. agonal state) and postmortem factors (e.g. fixation time), one should not only perform volume measurements, but also estimate a parameter that is not dependent on such factors as, i.e., total cell number of the brain structure in question. In addition, functional differences that depend on the levels of circulating hormones in adulthood have been observed in several hypothalamic and other brain structures. The mechanisms causing sexual differentiation of hypothalamic nuclei, the pre- and postnatal factors influencing this process, and the exact functional consequences of the morphological and functional hypothalamic differences await further elucidation.

Alzheimer Disease↗

Localization of serotonin-like immunoreactivity in the central nervous system and pituitary of the rat, with special references to the innervation of the hypothalamus.

The localization and distribution of serotonin (5-HT) has in the rat brain been studied with the indirect immunofluorescence technique of Coons (1958) using a newly developed, specific antibody to 5-HT. This paper contains a detailed description of the distribution of 5-HT in the hypothalamus and hypophyis and a brief report on the localization of 5-HT containing cell bodies. Principally, 5-HT perikarya were present in neuron systems with a distribution similar to that revealed by the mapping of Dahlström & Fuxe (1964) with the formaldehyde-induced-fluorescence technique (FIF). However, in addition to the nine areas originally described, several other areas in the mesencephalon and rhombencephalon appeared to contain 5-HT cell bodies. In the hypothalamus no 5-HT positive neuronal perikarya could be observed. However, in the infundibulum and in the median eminence some 5-HT positive tanycytes and mast cells were observed. Serotonergic fibers and terminals are present throughout the hypothalamus. Particularly dense plexus of the fibers and terminals have been observed in the lateral hypothalamic area, nucleus mamillaris medialis, the nucleus perifornicalis, the nucleus suprachiasmaticus and the nucleus ventromedialis hypothalami. All remaining hypothalamic areas demonstrate various densities of 5-HT immunoreactive nerve fibers. In the pituitary 5-HT-like immunoreactivity have been found in the pars nervosa.

Animals↗