Lesions Of Hypothalamic Paraventricular Nucleus Research Articles

Bilateral lesion of hypothalamic paraventricular nucleus abolishes fever induced by endotoxin and bradykinin in rats.

Annals of the New York Academy of SciencesVolume 856, Issue 1 p. 294-297 Bilateral Lesion of Hypothalamic Paraventricular Nucleus Abolishes Fever Induced by Endotoxin and Bradykinin in Ratsa JÉRRI C. CALDEIRA, JÉRRI C. CALDEIRA Laboratory of Neuroendocrinology, Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, BrazilSearch for more papers by this authorCELSO R. FRANCI, CELSO R. FRANCI Laboratory of Neuroendocrinology, Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, BrazilSearch for more papers by this authorIRENE R. PELÁ, Corresponding Author IRENE R. PELÁ Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil Address for correspondence: Irene R. Pelá, PhD, Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP. Av. do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil. Fax, 016 633 1092; e-mail, [email protected]Search for more papers by this author JÉRRI C. CALDEIRA, JÉRRI C. CALDEIRA Laboratory of Neuroendocrinology, Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, BrazilSearch for more papers by this authorCELSO R. FRANCI, CELSO R. FRANCI Laboratory of Neuroendocrinology, Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, BrazilSearch for more papers by this authorIRENE R. PELÁ, Corresponding Author IRENE R. PELÁ Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil Address for correspondence: Irene R. Pelá, PhD, Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP. Av. do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil. Fax, 016 633 1092; e-mail, [email protected]Search for more papers by this author First published: 07 February 2006 https://doi.org/10.1111/j.1749-6632.1998.tb08342.xCitations: 18 This study was supported by CNPq (Brazilian National Research Council, Project # 300751/96-6). Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume856, Issue1MOLECULAR MECHANISMS OF FEVERSeptember 1998Pages 294-297 RelatedInformation

Lesions of hypothalamic paraventricular nuclei do not prevent the effect of estradiol on energy and fat balance

The chronic effects of estradiol (E2) on energy balance have been investigated in ovariectomized rats with hypothalamic paraventricular nuclei (PVH) lesions. Body weight and food intake were monitored throughout the E2 treatment, which lasted 26 days. At the end of this treatment, rats were decapitated, and their carcasses were processed to determine the body contents in energy, fat, and protein. Plasma adrenocorticotropic hormone (ACTH) and corticosterone were determined by radioimmunoassay and protein-binding assay at the end of the study. Regardless of whether they were sham- or PVH-lesioned, E2-treated rats ate, expended, and gained significantly less energy than untreated animals. In addition, E2-treated rats deposited less fat and protein than the rats not receiving E2. In contrast to the E2 treatment, PVH lesions accelerated the gains in energy and fat regardless of whether the rats were treated with E2 or with a placebo. There were no interaction effects of PVH lesions and the E2 treatment on energy or fat gains. Plasma levels of corticosterone and ACTH were higher in E2-treated rats than in animals receiving the placebo treatment. The present results provide evidence that the hypothalamic PVH is not an essential neuroanatomical structure in the effects of E2 on energy and fat balances.

Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses

A number of receptor subtypes mediate hormonal responses to serotonin (5-HT). To test the hypothesis that the hypothalamic paraventricular nucleus (PVN) mediates 5-HT1A and 5-HT2 receptor-mediated oxytocin, PRL, and corticosterone responses, we studied the effects of the 5-HT1A agonist ipsapirone and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) after surgical PVN lesions or sham operations. Chronically cannulated, conscious, freely moving, male Wistar rats were injected iv (1 mg/kg) shortly after (3-4 days) and 5 weeks after (35-37 days) the operations. In sham-operated rats, ipsapirone caused marked elevations in plasma PRL and corticosterone, but not oxytocin concentrations, whereas DOI increased plasma concentrations of all three hormones. Short term PVN lesions prevented ipsapirone-induced corticosterone and DOI-induced oxytocin responses. DOI-induced PRL and corticosterone responses were also markedly inhibited 3-4 days after lesioning, although small rises over the baseline values were still observed. The ipsapirone-induced PRL response was unaffected by the lesioning. Five weeks after PVN lesioning, partial recoveries were observed in ipsapirone- and DOI-induced corticosterone and DOI-induced oxytocin responses, whereas DOI-induced PRL responses remained suppressed. The present findings suggest that the PVN or neural pathways close to it mediate oxytocin, PRL, and corticosterone responses to the 5-HT2 receptor agonist DOI as well as corticosterone, but not PRL, responses to the 5-HT1A receptor agonist ipsapirone. The results after long term PVN lesioning show that the oxytocin and corticosterone responses may be partially restored with time after lesioning.

Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses.

A number of receptor subtypes mediate hormonal responses to serotonin (5-HT). To test the hypothesis that the hypothalamic paraventricular nucleus (PVN) mediates 5-HT1A and 5-HT2 receptor-mediated oxytocin, PRL, and corticosterone responses, we studied the effects of the 5-HT1A agonist ipsapirone and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) after surgical PVN lesions or sham operations. Chronically cannulated, conscious, freely moving, male Wistar rats were injected iv (1 mg/kg) shortly after (3-4 days) and 5 weeks after (35-37 days) the operations. In sham-operated rats, ipsapirone caused marked elevations in plasma PRL and corticosterone, but not oxytocin concentrations, whereas DOI increased plasma concentrations of all three hormones. Short term PVN lesions prevented ipsapirone-induced corticosterone and DOI-induced oxytocin responses. DOI-induced PRL and corticosterone responses were also markedly inhibited 3-4 days after lesioning, although small rises over the baseline values were still observed. The ipsapirone-induced PRL response was unaffected by the lesioning. Five weeks after PVN lesioning, partial recoveries were observed in ipsapirone- and DOI-induced corticosterone and DOI-induced oxytocin responses, whereas DOI-induced PRL responses remained suppressed. The present findings suggest that the PVN or neural pathways close to it mediate oxytocin, PRL, and corticosterone responses to the 5-HT2 receptor agonist DOI as well as corticosterone, but not PRL, responses to the 5-HT1A receptor agonist ipsapirone. The results after long term PVN lesioning show that the oxytocin and corticosterone responses may be partially restored with time after lesioning.

Lesions of hypothalamic PVN partially attenuate stimulatory action of alcohol on ACTH secretion in rats

We have previously shown that the ability of alcohol to stimulate adrenocorticotropic hormone (ACTH) secretion was significantly blunted by immunoneutralization of endogenous corticotropin-releasing factor (CRF) and that long-term exposure to alcohol increased CRF mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus. In the present study, we further investigated the participating role of the PVN by studying the effect of bilateral lesions of the PVN on alcohol-induced ACTH release. The acute injection of alcohol (1.5 g/kg ip) induced significant increases in plasma ACTH levels in sham-operated animals. Lesions of the PVN attenuated this response but did not abolish it. Indeed, lesioned rats retained significantly elevated ACTH values despite removal of secretagogues of PVN origin. Because removal of hypothalamic CRF can alter ACTH secretion in response to secretagogues, we studied possible changes in pituitary responsiveness to CRF. The results failed to indicate that hyperresponsiveness of the corticotrophs played a major role in accounting for the residual ACTH release of lesioned rats after alcohol treatment. We conclude that brain regions other than the PVN can modulate ACTH release during acute administration of alcohol.

Hypothalamic paraventricular nuclear lesions delay corticotroph maturation in the fetal sheep anterior pituitary.

The purpose of this study was to determine whether normal morphological development occurs in pituitary corticotrophs deprived of products of the hypothalamic paraventricular nucleus (PVN), e.g. corticotropin releasing hormone and arginine vasopressin (AVP), after PVN lesions. In addition, we have attempted to ascertain if the neurophysin/AVP-positive fibers innervating the fetal sheep anterior pituitary are affected by PVN lesions. The experimental groups consisted of fetal sheep in which 1) hypothalamic PVN lesions were placed at 118-122 days gestation (dGA) and the fetuses subsequently harvested while still in utero at 157 dGA or more (PVNX; n = 5); 2) sham PVN lesions were placed at 118-122 dGA and subsequently harvested as newborn lambs immediately after birth at 146.5 +/- 0.9 (mean +/- SEM) dGA combined with two uninstrumented fetuses harvested at 144 dGA or more but not in labor (perinatal; n = 6); and 3) no instrumentation was placed, and the fetuses were harvested at 120 dGA (control; n = 4). Two ACTH-immunoreactive cell types were seen in the anterior pituitary: 1) fetal cells: large and variably stained, often columnar, occurring in clusters and arranged in palisades; and 2) adult cells: smaller, darkly staining, and angular, occurring singly or in small groups. Quantification of the distribution of the two ACTH cell types was performed by scanning sections from a one in six series from each pituitary and estimating the percent area of each section in the well that showed adult type staining only. The observer was blind to the treatment group assignment of the sections. The estimated percentages of the portion of the pituitaries of each group that contained adult-type cells only were as follows: PVNX, 42.8 +/- 10.0%; perinatal, 90.9 +/- 2.1%; and control, 3.7 +/- 1.1% (mean +/- SEM; P less than 0.05 for all comparisons). There were no qualitative differences between all groups in the appearance of neurophysin-positive fibers innervating the anterior pituitary. AVP staining was strong in the internal zone of the median eminence in all groups, but was absent in the external zone of PVNX fetuses only. The intermediate pituitary lobes stained darkly in all groups. We conclude that lesions of the PVN at 120 dGA delay development of fetal pituitary corticotrophs, but have no effect on the presence of neurophysin-positive nerve fibers in the anterior pituitary.

Hypothalamic paraventricular nuclear lesions delay corticotroph maturation in the fetal sheep anterior pituitary

The purpose of this study was to determine whether normal morphological development occurs in pituitary corticotrophs deprived of products of the hypothalamic paraventricular nucleus (PVN), e.g. corticotropin releasing hormone and arginine vasopressin (AVP), after PVN lesions. In addition, we have attempted to ascertain if the neurophysin/AVP-positive fibers innervating the fetal sheep anterior pituitary are affected by PVN lesions. The experimental groups consisted of fetal sheep in which 1) hypothalamic PVN lesions were placed at 118-122 days gestation (dGA) and the fetuses subsequently harvested while still in utero at 157 dGA or more (PVNX; n = 5); 2) sham PVN lesions were placed at 118-122 dGA and subsequently harvested as newborn lambs immediately after birth at 146.5 +/- 0.9 (mean +/- SEM) dGA combined with two uninstrumented fetuses harvested at 144 dGA or more but not in labor (perinatal; n = 6); and 3) no instrumentation was placed, and the fetuses were harvested at 120 dGA (control; n = 4). Two ACTH-immunoreactive cell types were seen in the anterior pituitary: 1) fetal cells: large and variably stained, often columnar, occurring in clusters and arranged in palisades; and 2) adult cells: smaller, darkly staining, and angular, occurring singly or in small groups. Quantification of the distribution of the two ACTH cell types was performed by scanning sections from a one in six series from each pituitary and estimating the percent area of each section in the well that showed adult type staining only. The observer was blind to the treatment group assignment of the sections. The estimated percentages of the portion of the pituitaries of each group that contained adult-type cells only were as follows: PVNX, 42.8 +/- 10.0%; perinatal, 90.9 +/- 2.1%; and control, 3.7 +/- 1.1% (mean +/- SEM; P less than 0.05 for all comparisons). There were no qualitative differences between all groups in the appearance of neurophysin-positive fibers innervating the anterior pituitary. AVP staining was strong in the internal zone of the median eminence in all groups, but was absent in the external zone of PVNX fetuses only. The intermediate pituitary lobes stained darkly in all groups. We conclude that lesions of the PVN at 120 dGA delay development of fetal pituitary corticotrophs, but have no effect on the presence of neurophysin-positive nerve fibers in the anterior pituitary.

Gastric motility and food intake in rats after lesions of hypothalamic paraventricular nucleus.

Systemic administration of cholecystokinin (CCK) or LiCl inhibits gastric motility and food intake in rats. Brain stem-projecting oxytocin (OT) neurons in the hypothalamic paraventricular nucleus (PVN) have been proposed to mediate the inhibitory effects of CCK and LiCl on gastric motility and food intake. In the present studies, we found that basal gastric motility was elevated in rats 12-20 h after knife-cut lesions of the PVN; however, this effect disappeared 3 days later. Furthermore, CCK and LiCl inhibited gastric motility at 12-20 h, 3 days, and 3 wk after PVN lesions, although their effects were blunted. Injection of the local anesthetic lidocaine into the PVN had effects similar to acute PVN lesions. In rats with PVN lesions, the inhibitory effects of CCK and LiCl on food intake were indistinguishable from those in sham-lesioned rats. We conclude that the PVN tonically inhibits gastric motility and that it participates in, but is not essential for, the inhibitory effects of CCK and LiCl on gastric motility and food intake in rats.

Homologous regulation of brain oxytocin receptors.

Specific receptors for oxytocin have been identified in rat forebrain. Previous studies have demonstrated that in select regions, these receptors are dependent on heterologous induction by gonadal steroids. To investigate whether brain oxytocin receptors are homologously regulated by oxytocin, we measured oxytocin receptor binding after hypothalamic paraventricular nucleus lesions, repeated central injections of oxytocin, and continuous central infusion of oxytocin via osmotic minipump. Neither lesions of the paraventricular nucleus nor repeated oxytocin injections altered the binding of the selective oxytocin receptor ligand [125I]OTA [125I] d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin, as measured by in vitro receptor autoradiography. After 10 days of continuous oxytocin infusion by osmotic minipump, oxytocin receptor binding decreased in every target field by at least 50%. This decrease appeared to represent a down-regulation of receptors and not displacement by exogenous peptide, as it persisted for at least 24 h after pump removal, and binding remained reduced in the presence of a saturating concentration of [125I] OTA. Reduction of oxytocin receptors in response to increased oxytocin release may represent an important physiological mechanism for the regulation of central oxytocin neurotransmission.

Hypothalamic paraventricular nucleus lesions do not prevent anorectic effect of exercise in male rats

The effects of a hypothalamic paraventricular nucleus (PVN) lesion on energy balance were investigated in exercise-trained rats. Male Wistar rats weighing initially 250 g were divided into four groups. Two groups of rats underwent a bilateral PVN lesion, whereas the two remaining groups were sham operated. The PVN lesions were done electrolytically. One group from each surgical treatment was exercised, while the other group was kept in sedentary conditions. Rats were exercised on a rodent motor-driven treadmill at moderate intensity, 1 h/day for 21 consecutive days. Food intake and body weight were measured each day during the study. At the end of the treatment period, rats were killed, and carcasses were analyzed for their energy content. Serum corticosterone was measured by a competitive protein-binding assay. Energy gain and energy intake were lower in exercised rats than in sedentary controls, regardless of whether they were sham or PVN lesioned. Concurrently, there was no difference in the energy gain between PVN-lesioned and sham-operated rats, despite the fact that PVN-lesioned rats ended the experiment with a larger body weight than the sham-lesioned animals. Serum corticosterone levels were lower in PVN-lesioned rats than in sham-lesioned rats. In conclusion, the present results indicate that the PVN, the hypothalamic nucleus predominantly controlling the pituitary-adrenal axis activity, is not a prominent structure in the regulation of energy balance in exercised male Wistar rats.

Increase of thyrotropin-releasing hormone immunoreactivity in the nucleus of the solitary tract following bilateral lesions of the hypothalamic paraventricular nuclei

The effects of bilateral electrolytic lesions of hypothalamic paraventricular nucleus on thyrotropin-releasing hormone (TRH)-immunoreactive fibers of the nucleus of the solitary tract were studied by both immunocytochemistry and radioimmunoassay. Contrasting with a near disappearance of TRH immunoreactivity in the median eminence, both morphological and biochemical approaches demonstrate that such hypothalamic lesions induced significant increase of TRH immunoreactivity in the nucleus of solitary tract. These results confirm that TRH fibers of the nucleus of the solitary tract do not originate in the hypothalamic paraventricular nucleus (PVN). They further indicate that these TRH neurons projecting to the nucleus of the solitary tract are strongly influenced by neurons located within the PVN area.

Reduction in cold-water swim analgesia following hypothalamic paraventricular nucleus lesions

The analgesic response following cold-water swims (CWS) has been shown to be mediated through neurohormonal mechanisms and independently of opioid systems. The hypothalamic paraventricular nucleus (PVN) appears to be important in autonomic, hypophysial and medial-basal hypothalamic function. The present study examined whether lesions placed in the PVN in rats would alter CWS analgesia on the tail-flick test. Animals with lesions placed in the PVN displayed significant reductions in analgesic magnitude 30 (66%) and 60 (54%) min following CWS relative to sham-treated rats without alterations in baseline latencies. In contrast, CWS analgesia was not altered in animals with lesions placed dorsal and/or lateral to the PVN. These data are discussed in terms of the roles of PVN projections to the median eminence and brainstem/spinal structures as well as roles for neurpopeptides in the PVN.

Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions

Noradrenergic mechanisms of the hypothalamic paraventricular nucleus (PVN) have been shown to play an important role in the stimulation of feeding To determine the influence of this nucleus in monitoring and controlling responses to physiological and pharmacological challenges, PVN electrolytic lesion rats were tested for their behavioral responsiveness to agents known to affect the α-2 noradrenergic system as well as release of corticosterone, and to short- and long-term periods of food deprivation. Discrete lesions of the PVN produced enhanced feeding, particularly of carbohydrate, in freely-feeding rats maintained on a macronutrient self-selection paradigm. Lesion rats demonstrated a behavioral deficit in food intake regulation (a decrease in carbohydrate ingestion) in response to 5-hr and 24-hr fasts, showed a disturbance in circadian feeding, and exhibited a dramatic decrease in circulating corticosterone. However, feeding in response to 2-deoxy-D-glucose and insulin remained intact, suggesting that noradrenergic receptors within the PVN are not involved in the mediation of glucoprivic-induced feeding.

Hypothalamic paraventricular nucleus lesions decrease pressor responses to subfornical organ stimulation

Electrical stimulation of the subfornical organ (SFO) in urethane anesthetized male Sprague-Dawley rats was associated with intensity and frequency dependent increases in arterial blood pressure. Stimulation in the hypothalamic paraventricular nucleus (PVN) also evoked increases in arterial blood pressure. Electrolytic lesions of the PVN significantly reduced SFO induced pressor responses, suggesting that the PVN constitutes part of the efferent pathways through which SFO stimulation elicits increases in blood pressure.

Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat

It has recently been demonstrated that chronic noradrenergic stimulation of the hypothalamic paraventricular nucleus (PVN) or wire knife cuts in the vicinity of the PVN cause hyperphagia and increased body weight. The present study investigates in rats the impact of electrolytic lesions within and around the PVN, on food intake, water intake, and daily body weight gain. Small lesions essentially restricted to the PVN are found to produce overeating and increased body weight, in both female and male rats maintained on either lab chow pellets or high fat mash. This effect appears to be strongest with lesions which damage the caudal aspect of the PVN. Destruction of tissue dorsal, ventral, or rostral to the PVN has no effect, or a suppressive effect, on food intake and body weight. With one exception, larger lesions, which extend beyond the borders of the nucleus, produce no greater response than lesions restricted to the PVN. The exception is a very large lesion which simultaneously damages the PVN and the ventromedial hypothalamic region (in the vicinity of the ventromedial nucleus) and which is somewhat more effective than PVN lesions in causing hyperphagia and obesity.