RESUMO
Methamphetamine (MA), a representative amphetamine-type stimulant, is one of the most abused drugs worldwide. Studies have shown that MA-induced neurotoxicity is strongly associated with oxidative stress and apoptosis. While nuclear factor E2-related factor 2 (Nrf2), an antioxidant transcription factor, is known to exert neuroprotective effects, its role in MA-induced dopaminergic neuronal apoptosis remains incompletely understood. In the present study, we explored the effects of MA on the expression levels of Nrf2, dynamin-related protein 1 (Drp1), mitofusin 1 (Mfn1), cytochrome c oxidase (Cyt-c), and cysteine aspartate-specific protease 3 (Caspase 3), as well as the correlations between Nrf2 and mitochondrial dynamics and apoptosis. Brain tissue from MA abusers was collected during autopsy procedures. An MA-dependent rat model was also established by intraperitoneal administration of MA (10 mg/kg daily) for 28 consecutive days, followed by conditioned place preference (CPP) testing. Based on immunohistochemical staining and western blot analysis, the protein expression levels of Nrf2 and Mfn1 showed a decreasing trend, while levels of Drp1, Cyt-c, and Caspase 3 showed an increasing trend in the cerebral prefrontal cortex of both MA abusers and MA-dependent rats. Notably, the expression of Nrf2 was positively associated with the expression of Mfn1, but negatively associated with the expression levels of Drp1, Cyt-c, and Caspase 3. These findings suggest that oxidative stress and mitochondrial fission contribute to neuronal apoptosis, with Nrf2 potentially playing a critical role in MA-induced neurotoxicity.
Assuntos
Apoptose , Metanfetamina , Dinâmica Mitocondrial , Fator 2 Relacionado a NF-E2 , Córtex Pré-Frontal , Animais , Metanfetamina/farmacologia , Metanfetamina/toxicidade , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Dinâmica Mitocondrial/fisiologia , Dinâmica Mitocondrial/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Masculino , Ratos , Humanos , Adulto , Ratos Sprague-Dawley , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Dinaminas/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/toxicidade , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/patologia , Pessoa de Meia-Idade , Adulto Jovem , FemininoRESUMO
Bone morphogenetic proteins (BMPs) are secreted signalling molecules belonging to the transforming growth factor-beta (TGF-beta) surperfamily. Up to date,more than 30 members of BMPs are identified. Bone morphogenetic protein-15 is only expressed in oocytes. Oocyte-specific BMP-15 might promote follicle growth in vivo, while preventing premature luteinization. This paper briefly discusses the progress in the research area of BMP-15 gene being as a candidate gene for litter size.
