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The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
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Binge alcohol drinking during adolescence has been associated with neurotoxicity and increased risk for the development of alcohol use disorders. There is evidence that acute and chronic ethanol administration alters c-fos expression, an indirect index of cellular activity, in different brain regions in adult rats. We evaluate here if a binge-like pattern of ethanol exposure during adolescence has a relevant impact on basal and/or ethanol-stimulated regional c-fos activity during adulthood. For that aim, Sprague-Dawley rats PND 25 were saline pre-treated, (SP group) or binge-ethanol pre-treated (BEP group) for twoconsecutive days, at 48-h intervals, over a 14-day period (PND 25 to PND 38). At adult stage (PND 63) and following 25 ethanol-free days, we evaluated c-fos immunoreactivity in response to saline or acute ethanol (1.5 or 3.0 g/kg) in the hypothalamus and amygdala. We found that acute ethanol administration dose-dependently increased c-fos activity in the the Paraventricular nucleus of the hypothalamus (PVN). Interestingly, binge-ethanol exposure during adolescence significantly reduced basal c-fos activity during adulthood in the Central nucleus of the amygdala (CeA) and the Arcuate nucleus of hypothalamus (Arc). We conclude that binge-like ethanol administration during adolescence causes long-term disturbances in basal neural activity in brain areas critically involved with ethanol consumption.
El consumo en atracón durante la adolescencia está asociado con neurotoxicidad y con el riesgo de desarrollar un trastorno en el uso de alcohol. Diversos estudios muestran que la administración aguda y crónica de alcohol en ratas adultas altera la expresión de c-fos, un marcador indirecto de actividad celular, en diferentes áreas cerebrales. Nosotros evaluamos si el patrón de consumo de alcohol en atracón durante la adolescencia tiene un impacto en la actividad basal de c-fos en esas regiones activadas por el alcohol. Utilizamos ratas Sprague-Dawley en su día post-natal 25 (PND25) tratadas con suero salino (grupo SP) o con etanol tipo atracón (grupo BEP) durante dos días consecutivos, en intervalos de 48 h, durante 14 días (PND25- PND38). En la edad adulta (PND63) y después de 25 días sin etanol, evaluamos la inmunorreactividad para c-fos en respuesta a una administración aguda de suero salino o etanol (1,5 ó 3,0 g/kg) en diferentes regiones cerebrales. La administración de alcohol incrementó de manera dosis-dependiente la actividad de c-fos en el núcleo paraventricular del hipotálamo. Además la exposición a etanol tipo atracón durante la adolescencia disminuyó la actividad basal de c-fos en la adultez en el núcleo central de la amígdala y en el núcleo arqueado del hipotálamo. Concluimos que el consumo de alcohol en atracón durante la adolescencia causa problemas a largo plazo en la actividad basal de regiones cerebrales implicadas en el consumo de alcohol.
Assuntos
Animais , Ratos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Etanol/administração & dosagem , Núcleo Central da Amígdala/efeitos dos fármacos , Imuno-Histoquímica , Fatores Etários , Etanol/farmacologiaRESUMO
Objective To observe the effect of microinjection of oxytocin(OT) into paraventricular nucleus(PVN) on gastric ischemia-reperfusion(GI-R) injury and its molecular mechanism.Methods GI-R injury was induced in rats by clamping the celiac artery for 30 min and followed by reperfusing for 1 h.A cannula was inserted into the unilateral PVN for microinjection of OT.The gastric mucosal injury index was counted grossly.The expressions of Akt and caspase-3 in rat gastric mucosa were examined by Western blot and by immunohistochemistry.Results Microinjection of OT into PVN dose-dependently allevated gastric mucosal injury subjected to GI-R.Microinjection OT into PVN significantly increased the expression of Akt protein and decreased the level of caspase-3 in gastric mucosal following GI-R.The effects of OT were prevented by pretreatment with OT receptor antagonist atosiban into the lateral cerebral ventricle.Conclusion Microinjection of OT into PVN significantly protected against GI-R injury.These effects of OT are mediated by its receptors.The mechanisms are mediated by increasing Akt expression,which in turn inhibits caspase-3 expression.
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Objective To observe effects of Apelin-13 microinjection into the hypothalamic paraventricular nucleus(PVN) on gastric ischemia-reperfusion(GI-R) injury in rats.Methods After Apelin-13 injection into PVN,the experimental model of GI-R was established by clamping the celiac artery for 30 min and then reperfused the artery for 1 h.We used immunohistochemistry to detect the gastric mucosal cells apoptosis,proliferation and the expression of BCL-2,BAX.Results(1)Apelin-13 microinjection into the PVN aggravated GI-R injury in an dose-dependent manner with dosages as 0.2,1.0 or 5.0 ?g,respectively.(2)Compared with GI-R group,Apelin-13 microinjection into PVN markedly increased gastric mucosal cellular apoptosis,decreased the proliferation and promoted protein expression of BAX,but obviously inhibited the protein expression of BCL-2.Conclusion Apelin-13 microinjection into the PVN may aggravate GI-R injury by promoting gastric mucosal cellular apoptosis and inhibiting proliferation.
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Objective To observe the effects of electrical stimulation of paraventricular nucleus(PVN) on gastric mucosal cellular apoptosis,proliferation,and expression of BCL-2,BAX induced by gastric ischemia-reperfusion(GI-R) and the potential mechanisms of protection of PVN on GI-R injury.Methods After electrical stimulation of PVN,the experimental model of GI-R were established by clamping the celiac artery for 30 min and then reperfusing the artery for 30 min,1 h,3 h,or 6 h respectively.We used immunohistochemistry to detect the gastric mucosal cells apoptosis,proliferation and the expression of BCL-2,BAX.Results Compared with GI-R group,the electrical stimulation of PVN markedly decreased gastric mucosal cellular apoptosis,increased the proliferation,and promoted the protein expression of BCL-2,but markedly inhibited the protein expression of BAX at 30 min,1 h,3 h after reperfusion respectively.Conclusion The protective effect of PVN on GI-R injury is associated with up-regulation of expression of BCL-2 and down-regulation expression of BAX,and so inhibited gastric mucosal cellular apoptosis and promoted proliferation.
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Dehydration induced an increase in plasma osmotic pressure that causes the release of the neurohypophysial hormone (Vasopresin, Oxytocin) which are synthesized in neurons of the paraventricular (PVN) and supra optic (SON) nuclei in the hypothalamus. On the other hand, PVN which plays an important role as an integration site for the neuroendocrine and autonomic nervous system neurons responded to osmotic stimulation. In this experiment, we studied that the change of several neuropeptidies (AVP: arginine vasopressin, CRF: cor-ticotrophin releasing factor, GAL: galanin, NT: neurotensin. NPY: neuropeptide Y) immunoreactivity in the PVN according to the dehydration. The body weight of the rats decreased during dehydration and various changes were detected in hypothalamic neuropeptidies immunoreactivity.Our results show that: 1. Dehydration significantly increased AVP, CRF and GAL immunoreactivity in the PVN. 2. Dehydration slowly decreased NT immunoreactivity in the PVN. 3. NPY immunoreactive cell bodys were appeared during dehydration which did not observed in PVN at normal group.
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Animais , Ratos , Arginina Vasopressina , Sistema Nervoso Autônomo , Peso Corporal , Desidratação , Galanina , Mãos , Hipotálamo , Imuno-Histoquímica , Neurônios , Neuropeptídeos , Neurotensina , Pressão Osmótica , PlasmaRESUMO
Microinjoction of thy-rotropin-releasing hormone (TRH) into par-avemricular nucleus (PVN ) obiviously increased gastric motility: frequency of gastric motility change from 3~1 times ? min-1 to 6 ~ 8 times ? min-1. intergastric pressure (IGP) rose from 0. 49 ? 0. 01kPa to 1. 9 1 ? 0. 5kPa. (P
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Objective:To study the possibility that responses of fever and c Fos expression in rat PVN and NTS to intraperitoneal administration of LPS are mediated by vagal afferents.Methods:Rectal temperature was detected by digital temperature detecting instrument.c Fos expression was detected by immunohistochemistry staining.Results:The rectal temperature change value in vagotomy LPS group was significantly decreased compared with that in sham LPS group,and there was striking difference between them,P