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PubMed1988

The history of thought concerning the hypothalamus and its functions.

Many initial studies related to identification of the boundaries and structural components, nuclei, tracts and interconnections of the hypothalamus; this continues. Early interest also focused on hypothalamic control of somatic activities and autonomic nervous system functions. During the present century chiefly, interest has developed in the hypothalamus and control of water balance, thirst, water retention and loss (diabetes insipidus and polydipsia). Its role in control of metabolism, body weight (obesity), and the regulation of body temperature has attracted the attention of physiologists for many years. Others have studied hypothalamic regulation of sex and reproductive phenomena. The hypothalamus is now attracting much attention because of its production of neuroendocrine secretions and role in control of the endocrine system. Physiologists realized very early that the hypothalamus is involved in emotional expression, in reaction to stress and adaptive adjustments. Its involvement in disease states and resistance thereto and in determining the nature of behavior has now been recognized as a matter of great importance. The origins of all these interests are reviewed.

Autonomic Nervous System↗
PubMed1995

Immunocytochemical localization of the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase, in the hypothalamus of cattle.

Immunocytochemical staining for the presence of catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase, was used to characterize the regional distribution of catecholaminergic neurons in the hypothalamus and adjacent areas of domestic cattle, Bos taurus. In steers, heifers and cows, tyrosine hydroxylase-immunoreactive perikarya was located throughout periventricular regions of the third cerebral ventricle, in both anterior and retrochiasmatic divisions of the supraoptic nucleus, suprachiasmatic nucleus, and ventral and dorsolateral regions of the paraventricular nucleus, dorsal hypothalamus, ventrolateral aspects of the arcuate nucleus, along the ventral hypothalamic surface between the median eminence and optic tract, and in the posterior hypothalamus. Immunostained perikarya ranged from small (10-20 microns, parvicellular) to large (30-50 microns, magnocellular) and were of multiple shapes: round, triangular, fusiform or multipolar, often with 2-5 processes of branched arborization. There were no dopamine-beta-hydroxylase immunoreactive perikarya observed within the hypothalamus and adjacent structures. However, both tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers and punctate varicosities were observed throughout regions of tyrosine hydroxylase immunoreactivity perikarya. Generally, the location and pattern of hypothalamic tyrosine hydroxylase immunoreactivity and dopamine-beta-hydroxylase immunoreactive were similar to those reported for most other large brain mammalian species, however, there were several differences with commonly used small laboratory animals. These included intense tyrosine hydroxylase immunoreactivity of perikarya within the retrochiasmatic division of the supraoptic nucleus (ventral A15 region), the absence of tyrosine hydroxylase immunoreactive perikarya below the anterior commissure or within the bed nucleus of stria terminalis (absence of the dorsal A15 region), an abundance of tyrosine hydroxylase immunoreactive perikarya within the ependymal layer of the median eminence, heavy innervation of the arcuate nucleus with dopamine-beta-hydroxylase immunoreactive fibers and varicosities, and the paucity of dopamine-beta-hydroxylase immunoreactive throughout the median eminence.

Animals↗
PubMed1996

Immunohistochemical mapping of nitric oxide synthase in the rat hypothalamus and colocalization with neuropeptides.

The localization and distribution of nitric oxide synthase in the hypothalamus have been studied with an immunohistochemical technique using antibodies to neuronal rat nitric oxide synthase. Subsequent double-labeling experiments examined the colocalization patterns of nitric oxide synthase and several peptides. Our results demonstrate a widespread occurrence of nitric oxide synthase-immunoreactive nerve cell bodies and processes throughout the hypothalamus, especially in various parts of the preoptic region, in the supraoptic and paraventricular nuclei, the lateral hypothalamic area, the ventromedial and dorsomedial nuclei, the arcuate nucleus and various parts of the mammillary region. Double labeling experiments showed that nitric oxide synthase-like immunoreactivity coexists with substance P-like immunoreactivity in the medial preoptic area, with oxytocin-, cholecystokinin-and galanin message-associated peptide-like immunoreactivity in the supraoptic nucleus, with enkephalin, oxytocin- and corticotropin releasing factor-like immunoreactivity in the paraventricular nucleus and with enkephalin-like immunoreactivity in the arcuate nucleus. Furthermore, in the ventromedial nucleus, nitric oxide synthase-like immunoreactivity coexisted with enkephalin-, substance P-, and somatostatin-like immunoreactivity, and in the dorsomedial nucleus with enkephalin-, galanin message-associated peptide-and substance P-like immunoreactivity. In the mammillary region nitric oxide synthase-like immunoreactivity coexisted with enkephalin-, cholecystokinin-, and substance P-like immunoreactivity. Among these neuropeptides, enkephalin and substance P were most frequently found in nitric oxide synthase-immunoreactive neurons. We conclude that nitric oxide synthase-immunoreactive neurons contain neuropeptides in various parts of the hypothalamus, and that nitric oxide in the hypothalamus may be involved in a variety of neuroendocrine and autonomic functions.

Animals↗
PubMed1994

Intracellular progesterone receptors are differentially regulated by sex steroid hormones in the hypothalamus and the cerebral cortex of the rabbit.

The aim of this study was to examine the role of sex steroid hormones in the regulation of intracellular progesterone receptors (PR) in the rabbit central nervous system. We determined PR concentration in cytosol preparations from the hypothalamus, the frontal, tempo-parietal and occipital cortex, by using the specific binding of the synthetic progestin [3H]ORG 2058. PR concentration was higher in the hypothalamus of intact adult females than in that of adult males and prepubertal females, whereas no significant differences were observed in the cerebral cortex of these animals. PR concentration was similar in the three cortical regions analyzed, indicating a homogeneous distribution of PR in the cerebral cortex. The administration of estradiol to ovariectomized animals increased PR concentration in the hypothalamus but not in the cortex. The administration of progesterone to ovariectomized rabbits did not modify PR concentration in any region, however when progesterone was administered after estradiol, it induced a significant diminution in hypothalamic PR concentration without effects in the cortex. These findings suggest that in the rabbit, PR are estrogen regulated in the hypothalamus but not in the cerebral cortex. In the latter, PR are not regulated by progesterone, whereas in the former the estrogen-induced PR are down-regulated by progesterone. Interestingly, hypothalamic PR constitutively expressed in ovariectomized animals are progesterone-insensitive.

Animals↗
PubMed2004

Postnatal ontogeny of natriuretic peptide systems in the rat hypothalamus.

Our study has attempted to clarify the developmental profile of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) along with the expression of their receptors in the rat hypothalamus. Radioimmunoassay (RIA) of dissected hypothalamic tissue revealed that ANP rose from 167 +/- 50 pg/mg protein immediately after birth to 516 +/- 78 pg/mg protein in the next 24 h and to 928 +/- 100 pg/mg protein by postnatal day (PD) 5. A second increment of ANP in the hypothalamus was noted between PD 10 and PD 20 (from 780 +/- 110 to 2,650 +/- 136 pg/mg protein). These changes were not gender-related and consistent with a rise of ANP mRNA. Diethylstilbestrol treatment of immature rats increased hypothalamic ANP concentration from 2.11 +/- 0.24 to 2.97 +/- 0.44 ng/mg protein (P<0.001), but equine chorionic gonadotropin had no effect, indicating that estrogen is a potential stimulus of ANP only at supra-physiological concentrations. CNP, the most abundant natriuretic peptide in the brain, gradually increased in the developing hypothalamus, but did not plateau at PD 20. Reverse transcription-polymerase chain reaction analysis of ANP receptor mRNA demonstrated higher guanylyl cyclase (GC) A, no changes in GC-B, and lower C-receptor levels in adult compared to newborn rats. In conclusion, we have shown that hypothalamic ANP undergoes a dramatic rise after birth, and progresses further until the 3rd postnatal week. ANP and CNP changes in the developing hypothalamus can influence brain maturation.

Animals↗
PubMed2004

Developmental expression of glucokinase in rat hypothalamus.

Neurons in the hypothalamus sense changes in glucose concentration. Glucokinase (GK), a key enzyme for pancreatic (beta)-cell glucose sensing, was found in both the embryonic and adult hypothalamus. GK activity accounted for approximately 20% of total hexokinase (HK) activity in both embryonic and adult hypothalamus with no activity measured in cortical samples, indicating that glucose sensing in the hypothalamus initiates early in development and precedes the maturation of glucose signaling in liver.

Age Factors↗
PubMed2005

A novel stereotaxic approach to the hypothalamus for the use of push-pull perfusion cannula in Holstein calves.

To determine secretory patterns of growth hormone-releasing hormone (GHRH) and somatostatin (SS) and their roles in the regulation of growth hormone (GH) secretion, a method for collecting hypothalamic perfusates, a push-pull perfusion method was developed in calves. With the use of the stereotaxic apparatus for cattle, a cannula was implanted into the hypothalamus of four male calves based upon cerebral ventriculography. Push-pull perfusates were collected at 10 min intervals for 6h and GHRH and SS concentrations in perfusates and plasma GH concentration were determined by EIAs and RIA, respectively. A cannula was implanted into the hypothalamus based on the image of the third ventricle and maintained for 1 month. GHRH and SS showed pulsatile secretion and the pulses for GHRH and SS were irregular in conscious animals. Neither GHRH nor SS secretion had a clear relationship with GH secretion. In the present study, we thus (1) established a stereotaxic technique for approaching the hypothalamus using cerebral ventriculography for calves, and (2) demonstrated that GHRH and SS secretion were pulsatile but not closely related to GH profile in conscious calves. The technique is useful for the study of the functions of the hypothalamus in the control of pituitary hormones in cattle.

Animals↗
PubMed2004

Effects of selective D1- or D2-like dopamine receptor antagonists with acute "binge" pattern cocaine on corticotropin-releasing hormone and proopiomelanocortin mRNA levels in the hypothalamus.

We have previously demonstrated that there are stimulatory effects of acute (1 day) "binge" cocaine on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamus and on the stress responsive hypothalamic-pituitary-adrenal (HPA) activity. The first aim of the present study was to investigate the possible role of dopamine (DA) D1- or D2-like receptors (D1R or D2R) in modulating these acute effects. Administration of acute "binge" cocaine (3x15 mg/kg, i.p.) was preceded by injections of either the selective D1R antagonist (SCH23390, 2 mg/kg) or D2R antagonist (sulpiride, 50 mg/kg). The D1R or D2R blockade by SCH23390 or sulpiride, respectively, did not alter the mRNA levels of CRH in the hypothalamus, CRH-R1 or proopiomelanocortin (POMC) in the anterior pituitary. However, the acute "binge" cocaine-induced increase in hypothalamic CRH mRNA levels was not found in the rats that received either D1R or D2R antagonist pretreatment. In the anterior pituitary, acute "binge" cocaine or its combinations with either DA antagonist did not alter CRH-R1 receptor or POMC mRNA levels. Both the D1R and D2R antagonists attenuated the elevation of plasma corticosterone levels induced by acute "binge" cocaine. These results suggest that both D1R and D2R mediate acute cocaine's stimulatory effect on HPA axis at the hypothalamic CRH level. Neurobiological evidence has demonstrated functional interactions between dopaminergic and opioidergic systems that regulate preproenkephalin and preprodynorphin gene expression in the striatum. The second aim of our study was to investigate the roles that D1R or D2R could play in regulation of POMC mRNA levels in the hypothalamus in response to acute "binge" cocaine. The D2R blockade by sulpiride increased POMC mRNA levels in the hypothalamus, indicating that D2R exerts a tonic inhibitory effect on hypothalamic POMC gene expression. The POMC mRNA increases induced by the D2R blockade were attenuated by acute "binge" cocaine. Neither the D2R blockade nor acute "binge" cocaine altered POMC mRNA levels in the amygdala, anterior pituitary or neurointermediate lobe of the pituitary. In contrast to the D2R, the D1R blockade by SCH23390, acute "binge" cocaine or their combination had no effect on hypothalamic POMC mRNA levels. These results support a specific role for D2R in acute cocaine's effects on hypothalamic POMC gene expression.

Amygdala↗
PubMed2006

Immunofluorescent identification of neuropeptide B-containing nerve fibers and terminals in the rat hypothalamus.

Neuropeptide B (NPB) and the structurally related neuropeptide W (NPW) have recently been identified as the endogenous ligands of the orphan G protein-coupled receptors GPR7 and GPR8. Whereas NPW is a high-affinity ligand for both GPR7 and GPR8, NPB activates only GPR7 in sub-nanomolar concentrations. GPR7 is highly conserved in both human and rodent orthologs while GPR8 has not been found in rodents. GPR7 mRNA is expressed in discrete regions of the hypothalamus suggesting a role in the regulation of energy homeostasis and neuroendocrine axes. In the present study, we have generated and extensively characterized antibodies that exert selective specificity for NPB. In dot-blot assays, these antibodies detected NPB but not NPW. Immunofluorescent staining of rat brain sections revealed moderately dense plexus of NPB-immunoreactive fibers and terminals in discrete areas of the hypothalamus. Neuronal somata were only seen in colchicine-treated rats. This immunostaining was completely abolished by preincubation of the antibodies with NPB but not with NPW. NPB-immunoreactivity was enriched in many regions within the hypothalamus which also contained high levels of GPR7 mRNA including the ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, supraoptic retrochiasmatic nucleus, and in the area ventral to the zona incerta. Together, NPB and its receptor GPR7 exist in close proximity in the rat hypothalamus and are, hence, ideally positioned to modulate neuroendocrine functions.

Animals↗
PubMed2004

5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

Adrenergic Uptake Inhibitors↗
PubMed2005

Enhanced nicotinic acetylcholine receptor-mediated [3H]norepinephrine release from neonatal rat hypothalamus.

Nicotinic acetylcholine receptor (nAChR)-evoked release of norepinephrine (NE) has been demonstrated in a number of brain regions that receive sole noradrenergic innervation from the locus coeruleus (LC). Many of these structures display enhanced nicotine-stimulated NE release in the neonate. We have examined the hypothalamus in order to determine if this region, which receives NE projections from both the LC and medullary catecholaminergic nuclei, also demonstrates maturational changes in nAChR-mediated NE release. Quantification of radiolabeled-NE release from rat hypothalamus slices by a maximally effective dose of nicotine revealed a peak response during the first postnatal week. This was followed by a decrease at postnatal day (P) 14, and a second peak at P21. Thereafter, release was equivalent to that observed at P14. Comparison of the pharmacological properties of nAChRs mediating NE release in neonatal (P7) and mature hypothalamus suggested involvement of different nAChR subtypes at the two ages. Using the selective toxin, DSP-4, nAChR-mediated NE release in the neonatal hypothalamus was shown to be from LC terminals. Our findings demonstrate an early sensitivity of hypothalamic LC terminals to nAChR regulation that may be associated with development of systems controlling critical homeostatic functions such as stress, feeding and cardiovascular regulation.

Aconitine↗
PubMed2005

Distribution of preprodynorphin mRNA and dynorphin-a immunoreactivity in the sheep preoptic area and hypothalamus.

Endogenous opioid peptides (EOP) are important modulators in a variety of neuroendocrine systems, including those mediating reproduction, energy balance, lactation, and stress. Recent work in the ewe has implicated the EOP, dynorphin (DYN), in the inhibitory effects of progesterone on pulsatile gonadotropin releasing hormone secretion. Although DYN is involved in a number of hypothalamic functions in the sheep, little is known regarding the localization of preprodynorphin (PPD) expression and its major product DYN A (1-17). In this study, we determined the distribution of PPD mRNA and DYN A-containing cell bodies in the brains of ovary-intact, luteal ewes. To detect PPD mRNA, an ovine PPD mRNA was subcloned by reverse transcription-polymerase chain reaction from sheep hypothalamus and used to create a (35)S-labeled riboprobe for in situ hybridization. Neurons that expressed PPD mRNA and DYN A immunoreactivity were widely distributed in the ovine preoptic area and hypothalamus. PPD mRNA-expressing cells were seen in the supraoptic nucleus, paraventricular nucleus, preoptic area, anterior hypothalamus area, bed nucleus of the stria terminalis, ventromedial nucleus (VMN), dorsomedial nucleus of the hypothalamus, and the arcuate nucleus. All of these regions also contained DYN A-positive cell bodies except for the VMN, raising the possibility that PPD is preferentially processed into other peptide products in the VMN. In summary, based on the expression of both mRNA and peptide, DYN cells are located in a number of key hypothalamic regions involved in the neuroendocrine control of homeostasis in sheep.

Animals↗
PubMed2005

Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia.

General anesthetics modulate autonomic nervous system function including thermoregulatory control, which resides in the preoptic area of the anterior hypothalamus. However, the mechanism by which anesthetics modulate hypothalamic function remains unknown. We hypothesized that isoflurane increases norepinephrine release in the preoptic area and in the posterior hypothalamus causing hypothermia during anesthesia. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo studies: 1) Norepinephrine release was measured by microdialysis in the preoptic area or the posterior hypothalamus (n=9 each) before, during (30 min), and after (50 min) rats were anesthetized with 2% isoflurane. 2) In five rats, blood gases and arterial pressure were measured. 3) Body temperature changes (n=6 each) were measured after prazosin (0, 0.05, 0.5 microg), norepinephrine (0, 0.1, 1.0 microg), or 0.5 microg prazosin with 1.0 microg norepinephrine injection into the preoptic area. In vitro study: Norepinephrine release was measured from anterior or posterior hypothalamic slices (n=10 each) incubated with 0, 1, 2, or 4% isoflurane in Ca2+-containing buffer or with 4% isoflurane (n=10) in Ca2+-free buffer. Data were analyzed with repeated measures or factorial ANOVA and Student-Newman-Keuls tests. P<0.05 was significant. During anesthesia, norepinephrine release in the preoptic area was increased approximately 270%, whereas the release in the posterior hypothalamus remained unchanged. During emergence, posterior hypothalamic norepinephrine release increased by approximately 250% (P<0.05). Rectal temperature changes correlated with norepinephrine release from the preoptic area. Norepinephrine in the preoptic area enhanced isoflurane-induced hypothermia, while prazosin reversed it. Norepinephrine release from anterior hypothalamic slices increased at all isoflurane concentrations, but only at the highest concentration in posterior hypothalamic slices. Under Ca2+-free conditions, 4% isoflurane increased norepinephrine from both regions. These results suggest that augmentation of norepinephrine release in the preoptic area is responsible for hypothermia during general anesthesia.

Anesthesia↗
PubMed2006

Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus.

Leptin, an adipocyte-derived hormone, reduces food intake by regulating orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived neurotrophic factor is an important anorexigenic factor in the hypothalamus, little is known about the regulation of brain-derived neurotrophic factor expression by leptin in the hypothalamus. In the present study, we examined the effect of leptin on the expression of brain-derived neurotrophic factor in the hypothalamus. I.V. administration of leptin (10 microg/g) led to the increase in the expression of brain-derived neurotrophic factor mRNA, which was observed in the dorsomedial part of the ventromedial hypothalamic nucleus. The increased expression of brain-derived neurotrophic factor mRNA was detected in phosphorylated signal transducer and activator of transcription 3-positive neurons, suggesting that leptin induced brain-derived neurotrophic factor expression in neurons of the dorsomedial part of the ventromedial hypothalamic nucleus. In addition, the expression of brain-derived neurotrophic factor was increased at the protein level in the ventromedial hypothalamic nucleus of leptin-injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers also increased in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus of leptin-injected mice, which were in close apposition to tyrosine kinase receptor B-immunoreactive neurons and colocalized with synaptophysin, a marker of presynaptic terminals. These results suggest that leptin induces brain-derived neurotrophic factor expression in the dorsomedial part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic factor may exert as anorexigenic factors possibly through the activation of tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus.

Animals↗
PubMed2004

Protective effect of pregnanolone against lipoperoxidation and free radicals generation induced in hypothalamus of ovariectomized rats submitted to CO2 exposure.

Several studies support an association between gonadal hormones and oxidative state. This study aimed to determine the consequence of the absence of ovarian hormones on the oxidative status of animals submitted to acute stress induced by CO(2) inhalation. We also evaluated the effect of pregnanolone administration upon the oxidative status in distinct brain structures of ovariectomized (OVX) rats exposed to CO(2). Female rats were divided into intact and OVX and exposed or unexposed to CO(2). Oxidative status was evaluated by 2',7'-dichlorofluorescein (DCF) assay, assessment of malondialdehyde (MDA), as an indicator of lipoperoxidation (through the thiobarbituric acid-reactive substances assay, TBARS), and the total antioxidant reactivity (TAR). Both DCF and TBARS were increased in the hypothalamus of animals submitted to OVX and stress. Nevertheless, free radical production and MDA levels were not affected in either condition alone. In the cerebral cortex, lower MDA levels were observed in OVX animals. Pregnanolone administered to rats submitted to CO(2)+OVX resulted in reduced MDA levels and free radicals production in hypothalamus. We suggest that ovarian hormones may protect the hypothalamus against oxidative stress, particularly when the animals are submitted to challenges. Pregnanolone may protect, at least in part, the hypothalamus of OVX rats from oxidative stress.

Animals↗
PubMed2004

Modulatory effect of endothelin-1 and -3 on neuronal norepinephrine release in the rat posterior hypothalamus.

Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the hypothalamus, we studied the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on neuronal norepinephrine (NE) release in the rat posterior hypothalamus. The intracellular pathways and receptors involved were also investigated. Neuronal NE release was enhanced by ET-1 and ET-3 (10 etaM). The selective antagonists of subtype A and B ET receptors (ETA, ETB) (100 etaM BQ-610 and 100 etaM BQ-788, respectively) abolished the increase induced by ET-1 but not by ET-3. The PLC inhibitor, U73122 (10 microM), abolished ET-1 and ET-3 response. GF-109203X (100 etaM) (PKC inhibitor) blocked the increase in NE release produced by ET-3 and partially blocked ET-1 response. The inositol 1,4,5-trisphosphate-induced calcium release inhibitor, 42 microM 2-APB, inhibited the stimulatory effect induced by ET-3 but not by ET-1. The PKA inhibitor, 500 etaM H-89, blocked the increase in neuronal NE release evoked by ET-1 but not by ET-3. Our results showed that ET-1 as well as ET-3 displayed an excitatory neuromodulatory effect on neuronal NE release in the rat posterior hypothalamus. ET-1 through an atypical ETA or ETB receptor activated the PLC/PKC signalling pathway as well as the cAMP pathway, whereas ET-3 through a non-ETA/non-ETB receptor activated the phosphoinositide pathway. Both ETs would enhance the sympathoexcitatory response elicited by the posterior hypothalamus and thus participate in cardiovascular regulation.

Animals↗
PubMed2003

Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance.

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Neuropeptide Y-immunoreactive (NPY-ir) structures in the brain of the gar Lepisosteus oculatus (Lepisosteiformes, Osteichthyes) with special regard to their anatomical relations to gonadotropin-releasing hormone (GnRH)-ir structures in the hypothalamus and the terminal nerve.

The present paper describes neuropeptide Y-like-immunoreactive (NPY-ir) structures in the brain of the spotted gar, Lepisosteus oculatus, with special regard to their anatomical relations to gonadotropin-releasing hormone (GnRH)-ir structures in the hypothalamus and the terminal nerve (TN). NPY-ir cells were found in various locations including the TN, the medial zone of the area dorsalis telencephali, the ventral nucleus of the area ventralis telencephali, the habenula, the dorsal posterior nucleus, the periventricular nucleus of the hypothalamus, the posterior tubercle, the optic tectum, and the lateral part of the tegmentum. NPY-ir fibers were widely distributed throughout the brain except for the cerebellum. They were locally dense in the ventral telencephalon, in the periventricular gray matter of the thalamus and the hypothalamus, and in the ventromedial part of the brainstem, but sparse in the olfactory system. Light-microscopic double immunohistochemistry demonstrated distinct NPY-ir and GnRH-ir structures in the ventral hypothalamus: the NPY-ir system was associated mainly with the periventricular gray matter, whereas the GnRH-ir system was prominent in the external zone of the preoptico-tubero-infundibular area including the median eminence (ME). Here, NPY-ir varicose fibers occasionally abutted on GnRH-ir cells and varicosities or invested GnRH-ir cells, suggesting that NPY directly regulates the function of the hypothalamic GnRHergic neuron system. On the other hand, the TN cells and fibers in the olfactory system were doubly labeled by the antibodies against NPY and GnRH. Immuno-electron-microscopic data strongly suggested that some of the TN fibers projected to the ME.

Animals↗