RESUMO
Brain areas expressing c-fos messenger RNA were mapped by quantitative in situ hybridization after 1-2 h of intoxication with 10 µg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, including the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus, locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NOstimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamic n. failed to induce penile erection, arguing against CNS involvement in this particular effect.
Assuntos
Encéfalo/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurotoxinas/toxicidade , Ereção Peniana/efeitos dos fármacos , Peptídeos/toxicidade , Proteínas Proto-Oncogênicas c-fos/metabolismo , Venenos de Aranha/toxicidade , Animais , Proteínas de Artrópodes/administração & dosagem , Proteínas de Artrópodes/química , Proteínas de Artrópodes/toxicidade , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/toxicidade , Relação Dose-Resposta a Droga , Hibridização In Situ , Injeções Intraventriculares , Masculino , Camundongos , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Neurônios/patologia , Neurotoxinas/administração & dosagem , Neurotoxinas/química , Especificidade de Órgãos , Peptídeos/administração & dosagem , Peptídeos/química , Proteínas Proto-Oncogênicas c-fos/agonistas , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/metabolismo , Agonistas de Canais de Sódio , Picada de Aranha/metabolismo , Picada de Aranha/patologia , Venenos de Aranha/administração & dosagem , Venenos de Aranha/químicaRESUMO
Brain areas expressing c-fos messenger RNA were mapped by quantitative in situhybridization after 12 h of intoxication with 10 mg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, includingthe supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus,locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NO stimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamicn. failed to induce penile erection, arguing against CNS involvement in thisparticular effect.
Assuntos
Camundongos , Aranhas/anatomia & histologia , Ereção Peniana , Neurotoxinas/administração & dosagem , Neurotoxinas/análise , Neurotoxinas/intoxicação , Neurotoxinas/toxicidade , Canais de Sódio , Cérebro/anatomia & histologia , Cérebro/fisiopatologia , Priapismo/induzido quimicamenteRESUMO
Orexins (hypocretins) have been implicated in the regulation of the normal sleep-wake cycle, in sensorimotor programming, and in other homeostatic and neuroregulatory processes. The present study examined the effects of sleep deprivation (SD) and sleep recovery on the expression of orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) throughout the brain. Rats were sacrificed either immediately after 96 h of sleep deprivation (SD group) or after SD followed by 24 h of sleep recovery (Rebound group). Prepro-orexin mRNA showed a non-significant increase in the SD group relative to controls, but a pronounced and significant increase in the Rebound group (+88%, P < 0.007). Similarly, sleep deprivation produced no effect on OX1R or OX2R mRNA levels. However, in the Rebound group, OX1R mRNA levels increased significantly, compared to either control or SD groups, in 37 of 92 brain regions analyzed, with particularly strong effects in the amygdala and hypothalamus. Changes in OX2R mRNA levels were also seen only in the sleep Rebound group, but they were fewer in number (10 out of 86 regions), were in the direction of decreased rather than increased expression, and were predominantly confined to cerebral cortical areas. These observations indicate that some factor associated with sleep recovery, possibly the compensatory increase in REM sleep, has strong effects on the orexin system at the mRNA level. They further indicate that,pOX1 and OX2 receptors are affected in opposite way and that the former are more vulnerable to these effects than the latter.
Assuntos
Encéfalo/metabolismo , Expressão Gênica/fisiologia , Receptores de Neuropeptídeos/metabolismo , Sono/fisiologia , Animais , Encéfalo/anatomia & histologia , Regulação da Expressão Gênica/fisiologia , Hibridização In Situ/métodos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Receptores de Orexina , Orexinas , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos/genética , Privação do Sono/metabolismo , Fatores de TempoRESUMO
Recent indications of oxidative stress in hypothalamus of sleep deprived rats prompted us to address the possibility that sleep deprivation may induce pathological cell loss changes in brain. Indices of necrosis and apoptosis were quantified after 96 h of sleep deprivation induced by the classical platform technique in rats. Binding of the "peripheral-type" benzodiazepine ligand [3H]PK 11195 to reactive astrocytes, a reliable and sensitive index of necrotic changes, was not altered in any of 14 brain regions examined. Likewise, no changes were found in mRNA levels of the apoptosis-related genes bcl-2 and bax in any of 24 brain regions examined. This was corroborated by quantitative TUNEL analyses in hypothalamus, amygdala, and cortex, which also revealed no effects in sleep deprived animals. These results are consistent with other recent evidence that sleep deprivation does not induce necrotic or apoptotic cell loss in brain. This suggests that recent findings of oxidative stress in sleep deprived brains do not result in cell loss. The possibility that sleep deprivation may result in functional deficits, or that structural changes may emerge after repeated episodes of sleep deprivation, remains to be addressed.