RESUMO
Several investigations have postulated evidence of the involvement of apoptosis in delayed neuronal death following brief periods of global cerebral ischemia. Apoptosis may be closely linked to mitochondrial dysfunction. Heat shock protein (HSP) 60 and HSP10 are mitochondrial matrix proteins induced by stress and form the chaperonin complex that is implicated in protein folding and assembly within the mitochondria. This study investigated the induction of these mitochondrial stress protein genes in the hippocampal CA1 region and less vulnerable regions following transient forebrain ischemia. In situ hybridization analysis revealed that the induction pattern of HSP60 mRNA was identical to that of HSP10 mRNA throughout the entire ischemic course. No changes occurred in the expression of both mRNAs after 2 min ischemia. Strong induction of both mRNAs occurred in the CA1 region after 10 min ischemia and persisted until 1 d after reperfusion. In contrast, induction of both mRNAs in the less vulnerable regions was terminated by 1 d after reperfusion. These results demonstrate that mitochondrial stress conditions persist concomitantly with cytosolic stress conditions in regions vulnerable to transient forebrain ischemia.
Assuntos
Isquemia Encefálica/genética , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Mitocôndrias/genética , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Animais , Apoptose , Northern Blotting , Isquemia Encefálica/patologia , Chaperonina 10/genética , Chaperonina 60/genética , Hipocampo/metabolismo , Hipocampo/patologia , Hibridização In Situ , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
The effect of middle cerebral artery (MCA) occlusion on the activity-regulated cytoskeleton-associated protein (Arc) mRNA expression has been investigated using in situ hybridization. It was induced in the extensive regions of cerebral cortex, medial striatum, and distant areas such as the ipsilateral lateral septal nucleus, bilateral hippocampal formation and contralateral amygdala following MCA occlusion. In the hippocampal formation, it was induced in the granule cell layer and the stratum pyramidale at 1 h and in the molecular layer and in the stratum oriens and stratum radiatum bilaterally at 4 h. MK-801 pretreatment strongly attenuated the induction of Arc mRNA. The present results suggest that Arc may play an important role in the neuronal plasticity through NMDA activation following focal cerebral ischemia.
Assuntos
Arteriopatias Oclusivas/complicações , Proteínas do Citoesqueleto/biossíntese , Dendritos/metabolismo , Genes Precoces , Ataque Isquêmico Transitório/metabolismo , Artéria Cerebral Média/patologia , Proteínas do Tecido Nervoso/biossíntese , RNA Mensageiro/biossíntese , Animais , Autorradiografia , Proteínas do Citoesqueleto/genética , Sondas de DNA , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hibridização In Situ , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/patologia , Masculino , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-DawleyRESUMO
Rheb is a recently identified member of the Ras super-family and is an immediate early gene that is rapidly and transiently induced in the hippocampal granule cells by NMDA-dependent synaptic activity in the long term potentiation paradigm. The close homologies with Ras and its rapid inducibility strongly suggest that Rheb shares many biochemical and signaling properties with Ras. The present study investigated the effect of middle cerebral artery (MCA) occlusion on the expression of Rheb mRNA in the rat brain. In situ hybridization autoradiography showed that Rheb mRNA was induced in the extensive regions of cerebral cortex and medial striatum surrounding the ischemic region and bilateral hippocampal formation following MCA occlusion. The induction of Rheb mRNA in the cingulate cortex persisted prominently at 24 h of MCA occlusion. Although the Rheb mRNA induction in the medial striatum and hippocampal formation decreased after 8h of occlusion, it still remained significant at 24h of occlusion. The data suggest the possibility that Ras signaling pathways can be implicated in the cerebral ischemia-elicited events through NMDA receptor activation.