Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats

Autor(es)

Maciel, Izaque de Sousa ; Sales, Amanda J. ; Casarotto, Plinio C. ; Castren, Eero ; Biojone, Caroline ; Joca, Samia R. L.

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Neuroscience; v. 55, n. 9-10, p. 14-pg., 2020-12-06.

Resumo

It has been postulated that the activation of NMDA receptors (NMDAr) and nitric oxide (NO) production in the hippocampus is involved in the behavioral consequences of stress. Stress triggers NMDAr-induced calcium influx in limbic areas, such as the hippocampus, which in turn activates neuronal NO synthase (nNOS). Inhibition of nNOS or NMDAr activity can prevent stress-induced effects in animal models, but the molecular mechanisms behind this effect are still unclear. In this study, cultured hippocampal neurons treated with NMDA or dexamethasone showed an increased of DNA methyltransferase 3b (DNMT3b) mRNA expression, which was blocked by pre-treatment with nNOS inhibitor n(omega)-propyl-l-arginine (NPA). In rats submitted to the Learned Helplessness paradigm (LH), we observed that inescapable stress increased DNMT3b mRNA expression at 1h and 24h in the hippocampus. The NOS inhibitors 7-NI and aminoguanidine (AMG) decreased the number of escape failures in LH and counteracted the changes in hippocampal DNMT3b mRNA induced in this behavioral paradigm. Altogether, our data suggest that NO produced in response to NMDAr activation following stress upregulates DNMT3b in the hippocampus. (AU)

• Processo FAPESP: 15/25067-6 - Avaliação do efeito dos inibidores da óxido nítrico sintase sobre a metilação do DNA e sobre a atividade e expressão das enzimas DNA metiltransferase em cultura de células de cérebro de rato
• Beneficiário: Izaque de Sousa Maciel
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 15/06271-1 - Avaliação do efeito dos inibidores da óxido nítrico sintase sobre a metilação do DNA e sobre a atividade e expressão das enzimas DNA metiltransferases no cérebro de ratos submetidos ao estresse
• Beneficiário: Izaque de Sousa Maciel
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático