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Undernutrition decreases serine palmitoyltransferase activity in developing rat hypothalamus.

BACKGROUND/AIMS: Undernutrition reduces the hypothalamic ganglioside concentration. This may be attributed to some modifications in the contents of precursors of sphingolipid biosynthesis in undernourished rats. The present study evaluated the serine palmitoyl transferase activity (SPT; EC 2.3.1.50) during the development of the rat hypothalamus. This work also shows the L-[3-(14)C]serine metabolic labeling of hypothalamic sphingolipids in normal and undernourished rats at weaning. METHODS: The SPT activity was determined in microsomal fractions obtained from the hypothalamus of normal rats (diet: 25% protein) and pre- and postnatally undernourished rats (diet: 8% protein since pregnancy) at 21 days of gestational age and at 7, 14, and 21 days of postnatal life. RESULTS: The enzymatic activity was lower in the hypothalamus of undernourished than in the hypothalamus of control rats since the 7th postnatal day. Incorporation of the precursor L-[3-(14)C]serine into sphingolipid fraction was lower in the hypothalamus of undernourished rats than in the hypothalamus of control rats on the 21st postnatal day which coincided with the age of the highest difference in SPT activity between normal and undernourished rats. CONCLUSION: These results indicate that undernutrition reduces the biosynthesis of the main sphingolipids during the period of brain growth spurt.

Acyltransferases↗

Endotoxin induces interleukin-1beta and nitric oxide synthase mRNA in rat hypothalamus and pituitary.

The gases nitric oxide (NO) and carbon monoxide (CO) may be involved in hypothalamo-pituitary-adrenal axis (HPA) modulation. In the brain, NO is synthesized by two forms of NO synthase (NOS), a constitutive neuronal form (nNOS) and an inducible form (iNOS). There are also a constitutive heme oxygenase (HO2) and an inducible form (HO1) which generate CO. We have therefore investigated the effect of peripheral lipopolysaccharide (LPS) administration on the gene expression of these enzymes along with interleukin-1beta (IL-1beta) gene expression in the hypothalamus, pituitary and liver. Male Wistar rats (200-250 g body weight) were injected intraperitoneally with endotoxin (Escherichia coli, 055 B5) dissolved in sterile normal saline [250 microg/kg first group, 2.5 mg/kg (second group) and 6.25 mg/kg (third group)] in a final volume of 0.5 ml, or saline alone in the control group. The first and the second groups were studied 1, 3, 8 and 24 h after LPS (n = 4 per group); the third group was studied at 3 h. Total RNA was extracted from the hypothalamus, pituitary and liver, and cDNA was made using standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of a specific gene in relation to the 'house-keeping' gene beta-actin. The specific genes studied were iNOS, nNOS, HO1, HO2 and IL-1beta. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. In the second group, iNOS and IL-1beta were induced in hypothalamus, pituitary and liver, showing a peak at 3 h (p < 0.001), returning to baseline levels at 24 h. Neuronal NOS was not expressed in the liver under basal conditions or after LPS; in the hypothalamus and pituitary, nNOS was expressed basally but there was no change after LPS. In the first group, iNOS and IL-1beta were again induced in all three tissues studied, but with a delayed time course compared to the second and third groups; the peak change for IL-1beta occurred at 8 h (p < 0.05), again returning to baseline levels at 24 h. The peak for iNOS occurred at 24 h. HO1 and HO2 were expressed in all three tissues under basal conditions; HO1 was increased at 1 h in the liver in the second group, and at 3 h in the pituitary in the third group. There was no change in either HO1 or HO2 in the hypothalamus at any dose at any time point. We conclude that IL-1beta and iNOS are induced in rat hypothalamus and pituitary following various doses of endotoxin. We speculate that while IL-1beta may mediate stimulation of the HPA by endotoxin, NO generation may be involved in the counter-regulation of this response.

Animals↗

Thalamic and midbrain auditory projections to the preoptic area and ventral hypothalamus in the green treefrog (Hyla cinerea).

Iontophoretic injections of horseradish peroxidase (HRP) into either the preoptic area or ventral hypothalamus of the green treefrog, (Hyla cinerea), demonstrated inputs from thalamic and midbrain auditory nuclei. In a pattern similar to that seen in Rana catesbeiana and Rana pipiens, the central thalamic and secondary isthmal nuclei were found to provide heavy input to the ventral hypothalamus. Additionally, a lighter input from the anterior thalamic nucleus was seen. In contrast, the preoptic area receives a major input from the anterior thalamic and secondary isthmal nuclei, and possibly a sparse input from the central thalamic nucleus. These results suggest that in treefrogs multimodal and auditory information may reach the preoptic area and ventral hypothalamus, two regions involved in endocrine regulation and the control of reproductive behavior, via largely separate major pathways from the thalamus combined with a common midbrain input. Furthermore, the ventral hypothalamus receives heavy input from the preoptic area, lateral amygdala, suprachiasmatic nucleus, anterior entopeduncular nucleus, and a lighter input from the striatum. Nonauditory afferents to the preoptic area originate in the medial and lateral septal nuclei, medial pallium, and the dorsal-, lateral-, and ventral hypothalamus. The preoptic area and ventral hypothalamus are reciprocally connected.

Animals↗

Effects of coincubation of the pituitary and hypothalamus of intact and castrate male rats and the influence of LH-RH on pituitary 5 alpha-reductase activity1,2.

Pituitary 5 alpha-reductase activity in intact male rats increases after the pituitary is incubated with the hypothalamus. Incubating the pituitary of castrate rats with the hypothalamus of intact rats relatively inhibits pituitary 5alpha-reductase activity. Coincubation of the pituitary and hypothalamus of castrate rats, or the pituitary of intact with the hypothalamus of castrate males, does not elicit changes in pituitary 5alpha-reductase activity. Different amounts of LH-RH in the incubation medium can modify 5alpha-reductase activity, i.e., activate it in the intact pituitary and inhibit it in the castrate pituitary. Hypothalamus from intact rats, which according to SHIN et al. [1974] is 'rich' in LH-RH, induces changes in pituitary 5alpha-reductase activity. The LH-RH-'poor' hypothalamus of castrate rats does not cause changes in this enzyme activity. The results suggest that there is a very close relationship between LH-RH and 5alpha-reductase activity in the pituitary.

Animals↗

In situ subcellular distribution and metabolism of progesterone, estradiol and androstenedione in the vascularly separated and isolated hypothalamus of the female rhesus monkey.

A neurosurgical procedure has been developed for the vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. The circulation to the left and right halves of the hypothalamus was also isolated and each half of the hypothalamus was perfused simultaneously, but separately, with a dextran-blood solution which contained radioactive gonadal steroids. The hypothalamus in situ efficiently converted [3H]androstenedione to [3H]estrone and this aromatization was inhibited by the presence of androsta-1,4,6-triene-3,17-dione (ATD) in the perfusate. [3H]Progesterone was metabolized predominantly to 5 alpha-pregnane-3,20-dione (5 alpha-DHP) and 20 alpha-hydroxypregn-4-ene-3-one (20 alpha-OHP). Subcellular fractionation of the hypothalamus after the in situ perfusion with [3H]-progestin or [3H]estradiol to the hypothalamus of estrogen-treated ovariectomized monkeys or oil-treated ovariectomized monkeys, respectively, indicated that the retention of [3H]estradiol in the nucleus was a saturable, limited-capacity phenomenon. No saturable subcellular distribution of [3H]progesterone or [3H]R 5020 was observed. This latter observation might be attributable to the presence of a progesterone receptor in too small a concentration to be detected by the methods used.

20-alpha-Dihydroprogesterone↗

Distribution of vesicular glutamate transporter-2 messenger ribonucleic Acid and protein in the septum-hypothalamus of the rat.

The excitatory neurotransmitter glutamate is involved in the control of most, perhaps all, neuroendocrine systems, yet the sites of glutamatergic neurons and their processes are unknown. Here, we used in situ hybridization and immunohistochemistry for the neuron-specific vesicular glutamate transporter-2 (VGLUT2) to identify the neurons in female rats that synthesize the neurotransmitter glutamate as well as their projections throughout the septum-hypothalamus. The results show that glutamatergic neurons are present in the septum-diagonal band complex and throughout the hypothalamus. The preoptic area and ventromedial and dorsomedial nuclei are particularly rich in glutamatergic neurons, followed by the supraoptic, paraventricular, and arcuate nuclei, whereas the suprachiasmatic nucleus does not express detectable amounts of VGLUT2 mRNA. Immunoreactive neurites are seen in very high densities in all regions analyzed, particularly in the preoptic region, followed by the ventromedial, dorsomedial, and arcuate nuclei as well as the external layer of the median eminence, whereas the mammillary complex does not exhibit VGLUT2 immunoreactivity. Many VGLUT2 immunoreactive fibers also contained synaptophysin, suggesting that the transporter is indeed localized to presynaptic terminals. Together, the results identify glutamatergic cell bodies throughout the septum-hypothalamus in region-specific patterns and show that glutamatergic nerve terminals are present in very large numbers such that most neurons in these brain regions can receive glutamatergic input. We examined the GnRH system as an example of a typical neuroendocrine system and could show that the GnRH perikarya are closely apposed by many VGLUT2-immunoreactive boutons, some of which also contained synaptophysin. The presence of VGLUT2 mRNA-containing cells in specific nuclei of the hypothalamus indicates that many neuroendocrine neurons coexpress glutamate as neurotransmitter, in addition to neuropeptides. These systems include the oxytocin, vasopressin, or CRH neurons as well as many others in the periventricular and mediobasal hypothalamus. The presence of VGLUT2 mRNA in steroid-sensitive regions of the hypothalamus, such as the anteroventral periventricular, paraventricular, or ventromedial nuclei indicates that gonadal and adrenal steroid can directly alter the functions of these glutamatergic neurons.

Animals↗

Neurotensin neurons in the rat hypothalamus: an immunocytochemical study.

Neurotensin was localized in the hypothalamic tissues of adult Sprague-Dawley rats by immunoperoxidase techniques. Visualization of perikarya was greatly enhanced by intraventricular administration of colchicine. Many perikarya containing neurotensin-like immunoreactivity were seen in the medial preoptic area, the periventricular hypothalamus, the parvocellular portion of the paraventricular nucleus, the arcuate nucleus, and the lateral hypothalamus in the perifornical area. There were moderate numbers of cell bodies in the ventral portion of the anterior hypothalamus, the dorsomedial nucleus, and the posterior hypothalamus. No positive cells were seen in the suprachiasmatic, ventromedial, or mammillary nuclei. Reactive fibers were generally distributed in the same regions as cell bodies. Additional dense collections were seen in the lateral part of the zona externa of the median eminence, the pituitary stalk, the posterior mammillary nucleus, and the most lateral portions of the hypothalamus at the medial edge of the crura cerbri. There were smaller numbers of fibers found in the pre-mammillary and posterior hypothalamic nuclei and the posterior pituitary gland. These results indicate that the neurotensin system in the hypothalamus is very extensive and complex, as it is in many other brain regions. Neurons and fibers are found in many hypothalamic areas, including projections to the hypophysial portal system in the median eminence, suggesting that neurotensin may affect neuroendocrine mechanisms at several levels, including the anterior pituitary gland.

Animals↗

Immunocytochemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid.

Insulin-like immunoreactivity (IRI) was detected in the rat hypothalamus, particularly in the paraventricular, periventricular, supraoptic, suprachiasmatic, arcuate, and lateral hypothalamic nuclei. The immunostainable IRI was diffusely distributed in comparison to the neuronal concentrations of immunostainable vasopressin in the periventricular nucleus, or of IRI in islet B cells, suggesting that immunostainable IRI in the hypothalamus is not concentrated in neuronal perikarya. To determine if insulin in cerebrospinal fluid (CSF) may be a source of some insulin in brain tissue, [125I]iodoinsulin was stereotaxically injected into a lateral cerebral ventricle, and the uptake of radioactivity into periventricular hypothalamus was localized by both quantitative autoradiography of paraffin-embedded brain sections and by measuring the radioactivity present in microdissected brain regions. In brains that received lateral ventricular injections of labeled insulin, the concentration of radioactivity in the periventricular region of the hypothalamus, as revealed by autoradiographic grains, was significantly greater than that in the periventricular region of brains that received lateral ventricular injections of labeled insulin mixed with an equimolar excess of an unlabeled peptide (insulin, ribonuclease, or both together). The highest levels of radioactivity detected in both autoradiographic and microdissection procedures were in regions nearest to the third ventricle, suggesting that insulin in the lateral ventricles has access to the periventricular neuropile in the hypothalamus. The staining pattern of immunostainable insulin in the hypothalamus along with the distribution of radioactivity after CSF injection of labeled insulin are consistent with the hypothesis that insulin is taken up into brain from the CSF.

Animals↗

Growth hormone-releasing factor immunoreactivity in the hypothalamus and cortex of the rat: in vivo and in vitro studies.

Utilizing a specific RIA for rat (r) GRF, hypothalamus and cerebral cortex from adult rat and long term dissociated fetal rat hypothalamic and cerebral cortical cell cultures were investigated for the presence of rGRF immunoreactivity (IR-GRF). After homogenization in an acidic medium, tissues and cultures were extracted on octadecylsilyl-silica columns, and IR-GRF and somatostatin (IR-SS) were measured by RIA. In extracts from the hypothalamus from the adult rat the content of IR-GRF was 3.02 +/- 0.16 ng ( +/- SE) per hypothalamus. IR-GRF was identical with synthetic rGRF on gel filtration chromatography and by parallel displacement of dilutions of extract in RIA. In extracts from cerebral cortex isolated from the adult rat, no IR-GRF was detected. In extracts from long term dissociated cell cultures from fetal hypothalami, 7.3 +/- 7 pg/10(6) cells of IR-GRF were present and were identical with synthetic rGRF by chromatographic and immunological criteria. In the extracts from cerebral cortical cell cultures cross-reacting material was present which on gel filtration chromatography revealed two peaks of immunoreactivity of higher mol wt than synthetic rGRF. There was nonparallelism on dilution of the extract. The ratio of IR-SS to IR-GRF by weight (IR-SS/IR-GRF) was calculated to compare the relative abundance of IR-GRF in cultured hypothalamic cells. In the hypothalamus isolated from the adult rat the ratio of IR-SS/IR-GRF by weight was 15.8 +/- 1.4 as compared to 48.9 +/- 10.3 in hypothalamic cultures. We conclude that IR-GRF indistinguishable from synthetic rGRF is present in long term dissociated hypothalamic cell cultures, but is relatively less abundant than in the hypothalamus of the adult rat when compared on the basis of IR-SS. No IR-GRF was detectable in cerebral cortex of the adult rat. At least one cross-reacting molecular species is detected in cerebral cortical cultures by the rGRF RIA, but exhibits nonparallelism and has a higher mol wt than synthetic rGRF. The increase of the ratio of IR-SS/IR-GRF in hypothalamic cell cultures in vitro compared to hypothalamus in vivo suggests that the culture conditions change differentially the expression of IR-SS and IR-GRF.

Animals↗

Insulin-induced hypoglycemia increases corticotropin-releasing factor messenger ribonucleic acid levels in rat hypothalamus.

To study the effect of acute stress on CRF release and synthesis in rat hypothalamus, ACTH levels in plasma, CRF contents in the median eminence (ME), and CRF mRNA levels in the hypothalamus without ME and cerebral cortex were determined after insulin-induced hypoglycemia. Plasma ACTH levels increased at 30 and 60 min, while ME CRF content decreased at 30 and 60 min, then returned to the control level at 90 min. Hybridization with a cRNA probe revealed a single size class of CRF mRNA in the hypothalamus and cerebral cortex (approximately 1300 nucleotides), and the size of CRF mRNA in these tissues did not change during the experimental period. CRF mRNA levels in the hypothalamus increased to 130% of the control value at 30 min and reached a peak (186% of the control value) at 120 min, but these levels in the cerebral cortex did not change. These results suggest that insulin-induced hypoglycemia stimulates CRF synthesis by increasing CRF mRNA levels in the hypothalamus as well as CRF release, and that release and synthesis of CRF in the cerebral cortex are independent of those in the hypothalamus.

Adrenocorticotropic Hormone↗

Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus.

GLP-1 has been shown to dramatically reduce food intake in fasted rats and is thought to exert its effects by modulating neuronal function in the hypothalamus. To date, little is known about the distribution of GLP1-R and its mRNA in the rodent hypothalamus. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP1-R mRNA in the rat hypothalamus. The results of these studies revealed an extensive distribution of GLP1-R mRNA throughout the rostral-caudal extent of the hypothalamus; with a dense accumulation of labeled cells in the supraoptic, paraventricular, and arcuate nuclei. Additional labeled cells were also detected in medial and lateral preoptic areas, periventricular nucleus, ventral division of the bed nucleus of the stria terminalis, lateral hypothalamus, and dorsomedial nucleus. The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP1-R mRNA in the rat hypothalamus. In addition, this morphological data provides important information about the neuronal systems modulated by GLP-1 and their potential role in feeding behavior.

Animals↗

Spontaneous expression of inducible nitric oxide synthase in the hypothalamus and other brain regions of aging rats.

Our laboratory has demonstrated that aging in Brown-Norway rats is associated with decreased LH pulse amplitude and reduced GnRH and LH responsiveness to excitatory amino acids (EAA), presumably through the NMDA receptor (NMDAR). Nitric oxide (NO) is a neurotransmitter postulated to be involved in hypothalamic synaptic events required for normal GnRH regulation through the activation of neuronal nitric oxide synthase (nNOS). Paradoxically, excessive stimulation of nNOS by NMDAR or the expression of inducible nitric oxide synthase (iNOS) can lead to supraphysiological levels of NO acting as effector of apoptosis with resultant decreased regional neuronal function. The aims of this study were to determine: 1) whether aging in the preoptic area/medial basal hypothalamus is associated with altered NO synthesis; 2) the possible roles of the NMDAR/nNOS cascade and iNOS in this process; and 3) whether alterations in the levels of NOS isoforms are specific to this region of the brain. Brown Norway male rats (N = 5) at ages 1 (immature), 3 (adult), and 24 (old) months, were used for measuring NMDARs in hypothalamic membranes by the binding of a (3H)-NMDAR ligand. Another series of the same age groups of rats (N = 9) were used to determine by Western blot the contents of NMDAR, nNOS, and iNOS in the hypothalamus, and only iNOS in the frontal and parietal cortex, and cerebellum. NOS activity was measured in the hypothalamus by the arginine/citrulline assay. A significant decrease of NMDA analog binding was found in the hypothalamus from old rats as compared with adult (-66%) and immature animals (-57%), accompanied by a reduction in NMDAR content (-34% and -46%, respectively). NOS activity in the hypothalamus was 67% and 100% higher in old rats as compared with the other two groups, although no significant differences were observed in nNOS content. However, hypothalamic iNOS increased 3.8- and 7.6-fold in old rats, as compared with adult and immature, respectively. This increase in hypothalamic iNOS was paralleled by a rise of iNOS in other brain regions of old rats as compared respectively to adult and immature animals: 3.9- and 12.8-fold, in the frontal cortex; 2.8- and 2.5-fold, in the parietal cortex; and 3.1- and 4.8-fold, in the cerebellum. These results show that aging in this rat model is associated with high NO synthesis in the hypothalamus and other regions of the brain, which is independent of the NMDAR/nNOS cascade. We speculate that increased brain levels of iNOS may lead to neurotoxicity, which may be involved in GnRH impaired pulsatile secretion, as well as acting as a possible inducer of age associated neuronal loss in cognitive related brain areas.

Aging↗

[Nuclei and fields of the rabbit hypothalamus].

Common features and distinctions in the structure of certain fields of the rabbit hypothalamus were established on the basis of cytoarchitectonical and cytological analysis. It has been shown that there are three types of nerve cells in the nuclei and fields of the hypothalamus which can be referred to somato-, cyto- and karyochromic elements of the nervous system in accordance with the Nissl classification. All the cellular structures of the hypothalamus can be divided into heteromorphic and isomorphic types. The medial and lateral hypothalamic fields of all the rostro-caudal length of the hypothalamus are referred to the first type. The hypothalamic nuclei occupying its basal part are referred to the second type. On the basis of the obtained data concerning the neuronal composition of the fields and nuclei of the hypothalamus, it can be divided into three zones: the medial zone, including 3 medial hypothalamic fields disposed along the 3d ventricle; the lateral zone comprizing two a lateral hypothalamic fields occupying its lateral parts along its all length and the basal zone including hypothalamic nuclei disposed mainly in the ventral part of the hypothalamus.

Animals↗

Localization of neuropeptide Y mRNA and peptide in the chicken hypothalamus and their alterations after food deprivation, dehydration, and castration.

Localization of neuropeptide Y (NPY) mRNA in the hypothalamus of chickens was studied by in situ hybridization with digoxigenin-labeled chicken NPY cRNA probe. The largest number of perikarya-expressing NPY mRNA was found within the mediobasal hypothalamus, including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence. Many NPY perikarya were noted to surround the nucleus rotundus and to be present in the supraoptic nucleus. Moreover, some perikarya were detected in the nucleus of basal optic root, bed nucleus pallial commissure, and nucleus striae terminalis close to the lateral forebrain bundle. NPY-immunoreactive nerve fibers were densely distributed in these regions containing the NPY mRNA-expressing perikarya. Following food deprivation for four days, perikarya-expressing NPY mRNA and peptide were markedly increased in the mediobasal hypothalamus and particularly so in the infundibular nucleus. No changes, however, were detected in other regions containing NPY-positive perikarya. Water deprivation induced less increase in NPY-positive perikarya in the mediobasal hypothalamus compared to food deprivation. After gonadectomy, the number of NPY-positive perikarya in the mediobasal hypothalamus was unaltered. Northern blot analysis with (32)P-labeled chicken NPY cDNA probe demonstrated that a 2.7-fold increase of NPY mRNA was induced by starvation and a 1.5-fold increase was induced by dehydration, whereas the NPY mRNA band remained unchanged after gonadectomy. Thus, it seems that NPY neurons located in the mediobasal hypothalamus are involved in feeding behavior but not reproductive activity.

Animals↗

Effects of low dose radiation on signal transduction of neurons in mouse hypothalamus.

OBJECTIVE: Effects of low dose radiation on signal transduction of neurons in mouse hypothalamus were investigated. METHODS: In the present study competitive protein binding assay, radioimmunoassay, in situ hybridization and immunohistochemistry were used to observe the effects of whole-body irradiation with 75 mGy X-rays on the contents of cAMP and cGMP and the expressions of c-fos mRNA, Fos protein and proopiomelanocortin (POMC) mRNA in the neurons of mouse hypothalamus. RESULTS: The results showed that cAMP content in mouse hypothalamus immediately increased significantly and reached the peak value in 15 min after irradiation, and then returned to near sham-irradiation level 1 h after irradiation, followed by a small fluctuation of increase and decrease; the changes of cGMP content were basically opposite to those of cAMP content, while the changes of cAMP/cGMP ratio were basically consistent with those of cAMP content. The expression of c-fos mRNA in the neurons of hypothalamus appeared 15 min after irradiation, reached its peak value within 1 h, began to abate 2 h with its total disappearance 8 h after irradiation; the expression of Fos protein reached its peak value 8 h after irradiation, and then gradually returned to sham-irradiation level 48 h after irradiation; the expression of POMC mRNA decreased significantly 1 h after irradiation and remained at a lower level in the observation period of 12 h. CONCLUSION: These findings implicate that low dose radiation may potentiate the activity of the neurons in mouse hypothalamus, expedite their signal transduction, and down-regulate the functions of hypothalamus-pituitary-adrenocortical axis.

Animals↗

The human hypothalamus: a morpho-functional perspective.

Historical investigation suggests that the role of the hypothalamus as a site of integration for endocrine with autonomic and behavioral responses in man rises from ideas and observations first appearing between the 14th and 18th centuries. Research on human, post-mortem brains and by in vivo magnetic resonance techniques reveal that the functional morphology of the hypothalamus in man is very similar to that in Rodents and Primates. As such, the adult human hypothalamus can be subdivided in three longitudinal zones, representing the source and target of neural informations traveling back and forth the brain stem, thalamus, limbic system, basal ganglia and neocortex. In addition, the human hypothalamus can be further partitioned in three anterior-posterior regions, of which the rostral one exerts a prominent regulation in predictive homeostasis, as opposed to the two caudal ones, primarily involved in reactive homeostasis. Finally, nuclear distribution in the human hypothalamus largely coincides with that in higher Mammals. Nevertheless, it is still unclear how the hypothalamus may give rise to specific homeostatic behaviors like hunger, thirst, reproductive and parental attitude, thermoregulation, aggressive-defensive performance, affective-motivational tone, circadian rhythmicity, sleep-wake cycle and immune regulation. The recent advent of new theories for nervous communication, like volume transmission and neural Darwinism, is progressively enlightening our understanding of the role played by the hypothalamic architecture in homeostatic responses, both in Mammals and man.

Afferent Pathways↗

[The effect of prolonged exposure to gamma rays and hormonal stimulation with serum gonadotropin on the levels of catecholamines in the hypothalamus, epiphysis and adrenal glands in sheep].

The effect of the exposure of the whole body to continuous radiation and of the administration of serum gonadotropin (SG) was studied as exerted on the concentration of catecholamines (epinephrine and norepinephrine) in the hypothalamus, epiphysis and adrenal glands of ewes during the anoestric period with synchronized oestrus. The first group (young barren ewes) and second group (older ewes) were exposed to continuous radiation of 60Co for five days. The radiation was provided at the rate of 0.020 Gy per hour. After the termination of irradiation the ewes were subjected to hormonal stimulation by fractionated administration of 1500 I. U. SG. The third and fourth experimental groups of ewes were stimulated with 1500 I. U. SG without irradiation. Catecholamines were separated from the tissue supernatants by the adsorption chromatographic method and the catecholamine contents in the eluates were determined spectrofluorometrically. Protracted exposure to gamma radiation and hormonal stimulation with SG reduces the concentration of norepinephrine in the whole hypothalamus of the sheep. A statistically significant decrease (P less than 0.001) was recorded in the medial and caudal hypothalamus of the adult ewes and in the rostral and caudal hypothalamus regions of the young ewes. A decrease of norepinephrine concentration, statistically significant in the caudal (P less than 0.01) and medial hypothalamus, was recorded in the group of adult ewes after hormonal stimulation with SG without irradiation. The experimental group of young ewes responds to hormonal stimulation by a greater reduction of norepinephrine contents, as compared with combined exposure to radiation and hormonal stimulation. It is assumed that the decrease in catecholamine concentration after hormonal stimulation with SG is associated with the increase in the content of oestrogens, which act on the adrenergic receptors of the hypothalamus.

Adrenal Glands↗

Effect of electrical and chemical stimulation of the lateral hypothalamus on taste preferences.

Bipolar stainless steel electrodes or stainless steel cannulas were implanted stereotaxically into the lateral hypothalamus of rats. Drinking was elicited by electrical or chemical (carbachol or angiotensin II) stimulation of animals, which were offered water and solutions of sodium chloride, saccharin, acetic acid and quinine. During electrical stimulation, ingestion of water and of all the solutions increased significantly. The same rats ingested significantly more sodium chloride and saccharin solution after 23 h water deprivation and electrical stimulation of the lateral hypothalamus. Carbachol administered into the lateral hypothalamus induced ingestion of saccharin solution and water but not of sodium chloride. Angiotensin II injected into the lateral hypothalamus did not induce drinking in most of the rats and those which drank preferred sodium chloride, saccharin and water. Several of the rats which did not respond to angiotensin II injection into the lateral hypothalamus, 72 h after angiotensin II responded to injection of carbachol by drinking the saccharin solution. The results of electrical stimulation suggest that the lateral hypothalamus consists of neurons involved in the ingestion of primary taste solutions. Depending on the functional state of the organism, lateral hypothalamic stimulation modifies ingestion of other taste substances but not of salt, as indicated by water deprivation. Chemical stimulation indicates that the neurotransmitter responsible for salt intake is not cholinergic and that the cholinergic neurons evoke preference for sweet taste and water. It appears that angiotensin II is involved in salt intake, as well as in producing preference for sweet taste and water.

Angiotensin II↗