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PubMed1991

Content and distribution pattern of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of neonatally estrogenized female rats.

The rostro-caudal distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of neonatally estrogenized (10 micrograms EB for 1-5 days), sterile female rats was compared with that of cycling rats at 50, 100 and 240 days of age. Serial slices of 400 microns in thickness in total were cut from a hypothalamic block, and the LHRH content of each slice was measured by radioimmunoassay. Two peaks of LHRH in the rostro-caudal direction were apparent in all groups. The rostral peak corresponded to the LHRH-producing cells in the septal-preoptic region and storage of LHRH in the organum vasculosum lamina terminalis (OVLT), while the caudal peak corresponded to that of LHRH in the median eminence. Thus, the total LHRH content of the regions of the hypothalamus was calculated separately either anterior or posterior to the suprachiasmatic nucleus, which were designated as the rostral hypothalamus (RH) and mediobasal hypothalamus (MBH), respectively. The total content of LHRH in the 50-day-old sterile rats was significantly higher than that in the estrous females in both RH and MBH. This was also true for the MBH of 240-day-old sterile females in comparison to that of estrous females but not so in 100-day-old females. The present results suggest that sterility in neonatally estrogenized rats is not due to a reduction in LHRH content of the hypothalamus but, rather, is due to changes in LHRH-releasing systems. Furthermore, in the control females, ovariectomy performed at 22 days of age induced a striking decrease in LHRH content in the MBH at 50 days of age, while it remained unchanged after ovariectomy in the neonatally estrogenized sterile rats. These findings suggest that the hypothalamic mechanism involved in the release of LHRH after ovariectomy was damaged by neonatal treatment with estrogen.

Analysis of Variance↗
PubMed1993

Neuropeptide Y increases the corticotropin-releasing factor messenger ribonucleic acid level in the rat hypothalamus.

Neuropeptide Y (NPY) has a stimulatory effect on adrenocorticotropin (ACTH) and corticotropin-releasing factor (CRF) release. In the present study, to investigate the effect of NPY on CRF synthesis, the effect of centrally administered NPY on CRF messenger RNA (mRNA) levels in rat hypothalamus was examined under pentobarbital anesthesia. The administration of 0.01, 0.1 and 1 nmol of NPY into the lateral ventricle dose-dependently Increased the plasma ACTH levels, as well as the levels of proopiomelanocortin mRNA in the anterior pituitary. The CRF mRNA level in the hypothalamus also increased after administration of 0.1 and 1 nmol of NPY in a dose-dependent manner. The administration of 3 nmol of phentolamine or propranolol failed to block 0.1 nmol NPY-induced ACTH release or 1 nmol NPY-stimulated CRF mRNA levels in the hypothalamus. These results Indicate that the central administration of NPY increases the CRF mRNA levels in the hypothalamus and the probable CRF release, which increases the proopiomelanocortin mRNA levels and ACTH secretion in the anterior pituitary. Therefore, NPY seems to play a physiological role in the regulation of the release and synthesis of CRF in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1983

Glucagon-induced somatostatin release from perifused rat hypothalamus: calcium dependency and effect of cysteamine treatment.

Somatostatin (SRIF) release from rat hypothalamus was investigated in vitro with a perifusion system. Glucagon (1 microM) and high potassium concentrations (56 mM) stimulated SRIF release in a calcium-dependent manner. Pretreatment of the rat with cysteamine (30 mg/100 g body weight, 7 h earlier) significantly reduced SRIF release from the hypothalamus in glucagon- and high potassium-stimulated states as well as in the basal state. SRIF release from rat hypothalamus was also stimulated by both dibutyryl cyclic AMP (1 mM) and theophylline (3 mM). These results suggest that glucagon, acting in a calcium-dependent manner and possibly through the adenylate cyclase-cyclic AMP system, stimulates SRIF release from rat hypothalamus and that cysteamine treatment reduces releasable SRIF in the hypothalamus.

Animals↗
PubMed1988

Opposite effects of ibotenic acid and 6-hydroxydopamine lesions of the lateral hypothalamus on intracranial self-stimulation and stimulation-induced locomotion.

The purpose of the present study was to test the respective roles of the intrinsic neurons and of the catecholaminergic fibers in two behaviors elicited by electrical stimulation of the lateral hypothalamus, intracranial self-stimulation and the increase in locomotor activity produced by noncontingent stimulation. One group of rats was unilaterally injected in the middle lateral hypothalamus with a dose of ibotenic acid known to significantly decrease self-stimulation (4 micrograms/0.5 microliter). Two other groups received, in the same area, an injection of a small dose of 6-hydroxydopamine (2 micrograms/0.5 microliter). The rats of one of these groups were pre-treated with desmethylimipramine. Two other groups of rats were respectively injected with the vehicle of each neurotoxin. Eight days later all rats were bilaterally implanted with stimulation electrodes, one in the lesioned area, the other in the contralateral region. Each electrode of each animal was tested first for self-stimulation, then for locomotor activation measured in the open field produced by non-contingent stimulation. Whatever the lesion or the behavior tested, the response of the lateral hypothalamus contralateral to the lesioned area was normal. Self-stimulation was disturbed only with stimulation of the lateral hypothalamus lesioned by ibotenic acid. Self-stimulation in the lateral hypothalamus lesioned by 6-hydroxydopamine was normal. However, a significant loss of noradrenaline in the hippocampus and of dopamine in the striatum was observed. Furthermore, the brains of two rats unilaterally injected with the usual dose of 6-hydroxydopamine were processed for tyrosine hydroxylase immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ontogenesis of tyrosine hydroxylase-immunopositive structures in the rat hypothalamus. An atlas of neuronal cell bodies.

The development of the catecholaminergic system in the hypothalamus and in the septal region was studied in rats from the 12th fetal day until the 9th postnatal day. Catecholaminergic structures were visualized with pre-embedding immunocytochemistry using antiserum to tyrosine hydroxylase. An intensification of diaminobenzidine product with silver and gold was additionally applied to make the immunocytochemical technique more sensitive. In this paper only the data on the appearance and distribution of the tyrosine hydroxylase-immunopositive neurons (cell bodies) are presented, whereas the catecholaminergic innervation of the hypothalamus with the tyrosine hydroxylase-immunopositive fibers is the topic of an accompanying paper. Sparse tyrosine hydroxylase-immunopositive neurons were first observed in the anlage of the hypothalamus and septal region on the 13th fetal day. Their number increased progressively with age and by the 15th fetal day they already gave rise to a large dorsal accumulation. From the 18th fetal day on, tyrosine hydroxylase immunopositive neurons began to occupy their definitive positions, mainly concentrating within the hypothalamus: in the zona incerta, periventricular and arcuate nuclei. To a lesser extent, they were concentrated in the medial preoptic area, suprachiasmatic, supraoptic, paraventricular, dorsomedial, and anterior hypothalamic nuclei. The data on the distribution of the tyrosine hydroxylase-immunopositive neurons both in the hypothalamus and in the septal region during ontogenesis are summarized in the precise atlas. Primarily small bi- and unipolar catecholaminergic neurons first observed in the youngest fetuses undergo cytodifferentiation during ontogenesis, giving rise to at least two different populations localized ventrally, mainly in the arcuate nucleus, and dorsally, in the zona incerta. The neurons of the former population remain similar to those of the youngest fetuses, whereas the neurons of the latter increase significantly in size, forming several long, highly ramified processes.

Aging↗
PubMed1990

Neurokinin A levels in the hypothalamus of rats and mice: effects of castration, gonadal steroids and expression of heterologous growth hormone genes.

Neurokinin A is a decapeptide with pharmacological activities and localizations similar to those of substance P. In this report we describe the effects of castration and administration of testosterone, dihydrotestosterone and estradiol, on neurokinin A levels in the hypothalamus of male rats. The effects of estradiol and testosterone on hypothalamic neurokinin A were also examined in normal mice and in transgenic mice carrying the genes for human or bovine growth hormone (hGH, bGH, respectively). Either acute or prolonged castration was followed by a decrease of neurokinin A concentrations in the hypothalamus of male rats. The substitutive administration of testosterone propionate or estradiol benzoate for 14 days resulted in an increase of hypothalamic neurokinin A levels above the values found in intact animals. A lower dose of testosterone propionate or dihydrotestosterone also increased hypothalamic neurokinin A levels in the hypothalamus of castrated rats. In normal intact male mice a single injection of estradiol benzoate significantly increased hypothalamic neurokinin A levels. A similar effect was observed in transgenic mice carrying the bGH gene with phosphoenolpyruvate carboxykinase (PEPCK) promoter, while mice carrying the hGH gene failed to show any response to estradiol. In castrated male mice, either normal or transgenic, carrying the bGH gene with metallothionein promoter, a single injection of testosterone propionate significantly increased neurokinin A levels in the hypothalamus. It is concluded that sex steroids may regulate the levels of neurokinin A in the hypothalamus of rats and mice.

Animals↗
PubMed1987

LHRH and beta-endorphin in the hypothalamus of the ram in relation to photoperiod and reproductive activity.

The regional distribution and relative concentrations of LHRH and beta-endorphin immunoreactivity in the hypothalamus were compared in sexually active and sexually inactive Soay rams. LHRH was localized principally in the medial basal hypothalamus and median eminence with lower concentrations in the anterior hypothalamus and preoptic area. beta-endorphin immunoreactivity was also found in highest concentrations in these regions but was more widely distributed into the rostral, dorsal and lateral parts of the hypothalamus. LHRH content in the medial basal hypothalamus was significantly lower in the sexually active rams compared to inactive rams while there was no difference in beta-endorphin immunoreactivity content between the two groups. Gel filtration chromatography of hypothalamic extracts revealed that the beta-endorphin immunoreactivity was due to both beta-lipotropin and beta-endorphin; the ratio of beta-endorphin: beta-lipotropin tended to be less in the sexually active rams than in the sexually inactive rams. The results are consistent with the hypothesis that beta-endorphin is a physiologically important endogenous opioid involved in the modulation of LHRH secretion.

Animals↗
PubMed1991

Effect of vasoactive intestinal peptide on the release of growth hormone in perifused pituitary and hypothalamus of the goat.

The effect of vasoactive intestinal peptide (VIP) on the release of growth hormone (GH) from the adenohypophysis of the goat was studied in vitro using the perifusion system. Two perifusion systems were employed to differentiate potential direct effects of VIP on the pituitary from indirect effects mediated through the hypothalamus. The first perifusion system used single chambers housing only pituitary fragments. The second system used two chambers in tandem, one containing hypothalamus and the second the pituitary fragments, the flow passing through the hypothalamic chamber first. VIP (10(-6), 10(-7), 10(-8)M) stimulated significant GH release in both perifusion systems (P less than 0.05, P less than 0.01) in a concentration related fashion. The quantity of GH release induced by the 10(-9)M and 10(-10)M VIP groups were not significant. Further, the GH released from the system that perifused the pituitary alone (10(-8)M VIP) was significantly higher than that containing both the hypothalamus and the pituitary fragments (P less than 0.05). The relative lower GH secretory response to the same dose of VIP applied to the hypothalamus-pituitary suggests that the perifused caprine hypothalamus may release an inhibitory factor, such as somatostatin in vitro. These results suggest that VIP stimulates GH release by acting directly on the adenohypophysis of the goat.

Animals↗
PubMed2006

Up-regulation of NPY gene expression in hypothalamus of rats with experimental chronic renal failure.

Anorexia is possibly one of the most important causes of malnutrition in uremic patients. The cause of this abnormality is still unknown. Considering that: (a) NPY is one of the most important stimulants of food intake; (b) eating is a central nervous system regulated process and (c) NPY is expressed in hypothalamus, we hypothesized that the decrease of NPY gene expression in the hypothalamus could be an important factor contributing to anorexia associated with uremic state. In contrast to the prediction, the results presented in this paper indicate that the NPY gene expression in the hypothalamus of chronic renal failure (CRF) rats was significantly higher than in the hypothalamus of control (pair-fed) rats. Moreover, we found that serum NPY concentration in CRF rats was higher than in control (pair-fed) animals. The increase of plasma NPY concentration in CRF rats may be due to the greater synthesis of the neuropeptide in liver, since higher level of NPY mRNA was found in liver of CRF rats. The results obtained revealed that experimental chronic renal failure is associated with the increase of NPY gene expression in hypothalamus and liver of rats.

Animals↗
PubMed2004

Cold exposure induces tyrosine phosphorylation of BIT through NMDA receptors in the rat hypothalamus.

The hypothalamus has a central role in maintaining homeostases of physiological conditions including body temperature and energy balance. To examine molecular responses to cold exposure in the hypothalamus, we examined changes in protein tyrosine phosphorylation in the suprachiasmatic nucleus of the hypothalamus after acute cold exposure in rats. It was found that brain immunoglobulin-like molecule with tyrosine-based inhibitory motifs (BIT, also called SHPS-1, SIRPalpha or p84), a transmembrane glycoprotein with two ITIM motifs, showed enhanced tyrosine phosphorylation after cold exposure. Its tyrosine phosphorylation induced by cold exposure was also found in other hypothalamic nuclei including the paraventricular nucleus, lateral hypothalamic area, ventromedial hypothalamus, and arcuate nucleus. This phosphorylation was blocked by AP-5, an NMDA receptor antagonist, indicating that it was mediated by NMDA receptors. These results suggest that BIT is involved in the mechanism of neuronal responses to cold exposure in the hypothalamus.

Amino Acid Motifs↗
PubMed2006

Estradiol reduces cumulative mercury and associated disturbances in the hypothalamus-pituitary axis of ovariectomized rats.

The aim of this research was to verify the incidence of endocrine dysfunction associated with mercury intoxication in the hypothalamus-pituitary reproductive system of normally cycling or castrated female rats and the possible protective action of estrogen replacement therapy. We found no differences in the frequency of estrus cycle stages (diestrus I, diestrus II, proestrus, and estrus) in normally cycling female rats during 54 days of daily oral administration of 0.004, 0.02, and 1 mg/kg MeHgCl. Conversely, the higher dose (1 mg/kg) induced a significant decrease in content of luteinizing hormone releasing hormone (LHRH) into the medial hypothalamus when administered daily during 3 days in ovariectomized rats. This effect was associated with increased levels of mercury found in the anterior pituitary gland and medial hypothalamus, rather than the anterior and posterior hypothalamus, striatum or cerebellum. A decrease in plasma levels of luteinizing hormone (LH) was also detected after administration of 7.5 mg/kg MeHgCl. These disturbances in LHRH and LH secretion induced by mercury were abolished or superimposed (respectively) by estrogenic replacement therapy (0.025 mg/kg 17beta estradiol cypionate, intramuscular). These effects were associated with a significant reduction in mercury content of the anterior pituitary gland and medial hypothalamus, suggesting a protective estrogenic effect.

Administration, Oral↗
PubMed2005

The top 10 most abundant transcripts are sufficient to characterize the organs functional specificity: evidences from the cortex, hypothalamus and pituitary gland.

Using serial analysis of gene expression, we have identified the most abundant mRNA transcripts in parietal cortex, hypothalamus and pituitary gland in adult male mice. High mRNA abundance of neurogranin (cell signalling and communication) was characteristic of the cortex. The common molecular features of cortex and hypothalamus were high abundance of mRNA encoding mitochondrial enzymes such as reduced form of nicotinamide adenine dehydrogenase (NADH) 4 and cytochrome c oxidase 2 (energy metabolism), brain creatine kinase (energy metabolism) and myelin basic protein (cell structure). In the hypothalamus, mRNA levels of apolipoprotein E (lipid metabolism), prostaglandin D2 (cell signalling and communication) and secreted acidic cysteine-rich glycoprotein (extracellular matrix) were especially high. A common molecular feature of the hypothalamus and pituitary was high mRNA abundance of guanine nucleotide binding protein alpha stimulating complex locus (cell signalling and cell communication). The pituitary gland was characterized by high expression of genes encoding hormones such as growth hormone, pro-opiomelanocortin and prolactin, as well as neuronatin (cell differentiation) and four potential novel transcripts. Thus, these results show that the cortex, hypothalamus and pituitary gland can be specifically characterized according to their 10 most abundant transcripts. In addition, the current study serves as a basis for future studies on the potential novel transcripts and the transcripts with unclear functions despite their extremely high abundance, as well as studies on physiology and pathology of the two brain regions and pituitary gland.

Animals↗
PubMed2003

Hypothalamus of the human fetus.

The organization of the human hypothalamus was studied in 31 brains aged from 9 weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin, calbindin, calretinin, neuropeptideY, neurophysin, growth associated protein GAP43, synaptophysin and glycoconjugate, 3-fucosyl-N-acetyl-lactosamine. Morphogenetic periods 9-10 and 11-14 w.g. are characterized by differentiating structures of the lateral hypothalamic zone, which give rise to the lateral hypothalamus (LH) and posterior hypothalamus. The perifornical nucleus differentiates at 18 w.g., from LH neurons which remain anchored in the perifornical position while 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, the dorsomedial and the shell were revealed by distribution of calbindin, calretinin and GAP43 immunoreactivity. Morphogenetic periods 15-17, 18-23 and 24-33 w.g. are 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. Morphogenetic period after 34 w.g. was marked by differentiation of midline zone structures including suprachiasmatic, arcuate and paraventricular nuclei. The findings of the present study provide for a better understanding of the structural organization of the adult human hypothalamus, produce new evidence for homologies with the better studied rat hypothalamus and underpin staging system for fetal human hypothalamic development.

Animals↗
PubMed2005

Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats.

The aging process is associated with cognitive impairment and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress. We determined some parameters of oxidative stress in homogenates of hippocampus, hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A significant age-dependent increase in the generation of free radicals was observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx) activity was significantly reduced in hypothalamus and hippocampus from 6-months-old rats; a decline on GPx and catalase activities in adrenal glands of 24-months-old animals was also present. Interestingly, a great decrease in total antioxidant capacity was found in all tissues tested. Reported findings support the idea that oxidative events participate on multiple neuroendocrine-metabolic impairments and suggest that the oxidative stress found in hippocampus, hypothalamus and adrenals might be associated with age-related physiological deficits.

Adrenal Glands↗
PubMed2003

Differences between natriuretic peptide receptors in the olfactory bulb and hypothalamus from spontaneously hypertensive and normotensive rat brain.

Natriuretic peptide receptor-A (NPR-A) functional characteristics in the hypothalamus and olfactory bulb (OB) have been investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Autoradiographic studies demonstrate a decreased number of atrial natriuretic peptide (ANP) binding sites in the olfactory bulb and hypothalamus in SHR compared to WKY rats. We found that NPR-A showed a lower maximal binding capacity (B(max)) and higher affinity in SHR than in WKY rats both in the olfactory bulb and hypothalamus. However, despite the lower B(max) in SHR, both ANP(1-28) and ANP(5-25) stimulated similar or greater cGMP production than in WKY rats. These differences were found even before the development of hypertension. NPR-A in the olfactory bulb and hypothalamus from 3-week-old SHR showed a lower B(max) and K(d) and a higher cGMP production rate than in WKY rats, suggesting that these characteristics are intrinsic of NPR-A in SHR, instead of being a result of hypertension itself. The present study provides evidences for altered NPR-A receptor properties and function in the olfactory bulb and hypothalamus from SHR, which might be involved in the pathogenesis of hypertension.

Animals↗
PubMed2005

3,4-Methylenedioxymethamphetamine increases pro-interleukin-1beta production and caspase-1 protease activity in frontal cortex, but not in hypothalamus, of Dark Agouti rats: role of interleukin-1beta in neurotoxicity.

3,4-Methylenedioxymethamphetamine (ecstasy) increases mature interleukin-1beta production in rat brain shortly after injection. This effect is a consequence of the 3,4-methylenedioxymethamphetamine-induced hyperthermia and is reduced when rats are maintained at low ambient room temperature. Since interleukin-1beta is generated as an inactive 31-kDa precursor protein and processed into mature form by caspase-1, we have now examined the effect of 3,4-methylenedioxymethamphetamine on pro-interleukin-1beta production and caspase-1-like protease activity in the hypothalamus and frontal cortex of Dark Agouti rats. 3,4-Methylenedioxymethamphetamine increased the immunoreactivity of pro-interleukin-1beta in frontal cortex, not in hypothalamus, 3 h and 6 h after administration. Caspase-1-like protease activity was increased in frontal cortex 3 h after 3,4-methylenedioxymethamphetamine injection compared with saline-treated animals. 3,4-Methylenedioxymethamphetamine did not modify the expression of pro-caspase-1 but increased the immunoreactivity for the caspase-1 active cleavage product (p20) in frontal cortex 3 h after dosing. No change on caspase-1-like protease activity was observed in hypothalamus. The basal immunoreactivity of pro-interleukin-1beta and caspase-1-like protease activity was higher in the hypothalamus than in frontal cortex of control (saline-treated) animals. These data indicate that 3,4-methylenedioxymethamphetamine alters, in a region-specific manner, the mechanisms which regulate interleukin-1beta production in the brain of Dark Agouti rats and suggest that the release of interleukin-1beta in hypothalamus may be regulated independently of caspase-1 activation. Administration (i.c.v.) of interleukin-1beta enhanced the 3,4-methylenedioxymethamphetamine-induced long-term loss of brain 5-HT parameters and immediate hyperthermia. Neither of these effects was observed when interleukin-1beta was given into hippocampus. These results indicate that exogenous interleukin-1beta potentiates 3,4-methylenedioxymethamphetamine neurotoxicity as a consequence of its effect on body temperature and suggest that the 3,4-methylenedioxymethamphetamine-induced rise in interleukin-1beta levels could in turn contribute to the maintenance of 3,4-methylenedioxymethamphetamine-induced hyperthermia and subsequent neurotoxicity.

Animals↗
PubMed2005

The reciprocal connections of endomorphin 1- and endomorphin 2-containing neurons between the hypothalamus and nucleus tractus solitarii in the rat.

In the CNS, endomorphin 1- and endomorphin 2-immunoreactive neuronal cell bodies have been principally found both in the hypothalamus and nucleus tractus solitarii. Functionally, the hypothalamus and nucleus tractus solitarii are closely related in many aspects, especially in visceral functions. On the other hand, there are also many endomorphin-immunoreactive fibers and terminals in the two regions. In the present study, to investigate whether endomorphin 1-immunoreactive and endomorphin 2-immunoreactive neurons in the hypothalamus and nucleus tractus solitarii project reciprocally between these two regions, fluorescent retrograde labeling combined with immunofluorescence histochemical staining for endomorphin 1 and endomorphin 2 was used. After injection of Fluoro-Gold into the nucleus tractus solitarii of rats, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were predominantly observed in the arcuate nucleus of the hypothalamus, a few of which were also observed in the posterior hypothalamic area and periventricular hypothalamic nucleus. After injection of Fluoro-Gold into the medial zone of hypothalamic tuberal region and the lateral hypothalamic area, respectively, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were found chiefly in the medial, commissural, lateral and gelatinous parts of the nucleus tractus solitarii. These results provide morphological evidence that there exist reciprocal endomorphinergic connections between the hypothalamus and nucleus tractus solitarii.

Animals↗
PubMed2006

Profiles of novel diurnally regulated genes in mouse hypothalamus: expression analysis of the cysteine and histidine-rich domain-containing, zinc-binding protein 1, the fatty acid-binding protein 7 and the GTPase, ras-like family member 11b.

Gene expression profiling of suprachiasmatic nucleus, ventrolateral preoptic area and the lateral hypothalamus was used to identify genes regulated diurnally in the hypothalamus of Mus musculus. The putative transcription regulator, cysteine and histidine-rich domain-containing, zinc binding protein 1, which had not been previously described in brain, was found to cycle diurnally in hypothalamus and forebrain with peak levels of mRNA expression during the dark phase. mRNA for the brain-type fatty acid binding protein 7 was found to change rhythmically in hypothalamic and extra-hypothalamic brain regions reaching peak levels early in the light phase suggesting that lipid metabolism is under circadian regulation in astrocytes. Rhythmically expressed genes in suprachiasmatic nucleus identified here were compared with previous reports in a meta-analysis. Genes held in common included fabp7, and the period gene, Per2. Also identified were genes implicated in guanosine-mediated signaling pathways that included dexamethasone-induced ras-related protein one (dexras1), regulator of G-protein signaling (rgs) 16, and ras-like family member 11b. Northern blotting confirmed diurnal changes in mRNA expression in the hypothalamus for these genes. Ras-like family member 11b was examined in more detail using in situ hybridization and antiphase diurnal changes in expression in suprachiasmatic nucleus and arcuate nucleus were identified implicating the gene in circadian-related, guanosine-mediated signaling. The transcription transactivator protein, CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain, which had not been previously identified in brain, was enriched in suprachiasmatic nucleus and discrete regions of the hypothalamus and forebrain. The potential regulatory role of CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain in the transcription of genes like TGF-alpha implicates the protein in diurnal activity rhythms. These results demonstrate the ability of gene expression profiling to identify potential candidates important in circadian or homeostatic processes.

Animals↗