RESUMO
Amyloid-ß peptides (Aß), which can aggregate into oligomers or fibrils in neurons, play a critical role in the pathogenesis of Alzheimer's disease (AD). Methyl 3,4-dihydroxybenzoate (MDHB), a phenolic acid compound, has been reported to have antioxidative and neurotrophic effects. The present study investigated the neuroprotective effects of MDHB against Aß-induced apoptosis in rat primary cortical neutons. The primary cortical neurons were pretreated with different concentrations of MDHB for 24 hr, then incubated with 10 µM Aß25-35 for 24 hr. The results showed that Aß25-35 could induce neurotoxicity as evidenced by the decreased cell viability and the increased apoptotic rate. In parallel, Aß25-35 significantly increased the reactive oxygen species accumulation and decreased mitochondrial membrane potential. However, pretreatment of the primary cortical neurons with MDHB could effectively suppress these cellular events caused by Aß25-35 exposure. In addition, MDHB could increase the level of Bcl-2, decrease the level of Bax, and inhibit the activation of caspase-9 and caspase-3 in Aß25-35 -treated primary cortical neurons. All these results were beneficial in their protective effect against Aß-induced neurotoxicity. Our results suggest that MDHB has a neuroprotective effect that provides a pharmacological basis for its clinical use in the treatment of AD.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Hidroxibenzoatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Análise de Variância , Animais , Animais Recém-Nascidos , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Líquido Intracelular/efeitos dos fármacos , Líquido Intracelular/metabolismo , Metaloproteinases da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
In this study, we evaluated the neurotrophic effects of magnesium fructose 1, 6-diphosphate (FDP-Mg) on cortical neurons. The results demonstrated that FDP-Mg promoted dendrite outgrowth and neuronal survival in a dose-dependent manner. In order to investigate the associated mechanisms, we determined adenosine triphosphate (ATP) levels and brain-derived neurotrophic factor (BDNF) mRNA expression in cortical neurons. Treatment with FDP-Mg significantly increased ATP levels and BDNF mRNA expression in cortical neurons. These data suggest that FDP-Mg can exert neurotrophic effects on cortical neurons. The increases in BDNF mRNA expression and cellular ATP levels are involved in the neurotrophic effects produced by FDP-Mg.