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Neurotoxicology ; 84: 1-13, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33549657

RESUMO

Accumulating evidences suggest that inflammation-mediated neurons dysfunction participates in the initial and development of Parkinson's disease (PD), whereas mitochondria have been recently recognized as crucial regulators in NLRP3 inflammasome activation. Cordycepin, a major component of cordyceps militaris, has been shown to possess neuroprotective and anti-inflammatory activity. However, the effects of cordycepin in rotenone-induced PD models and the possible mechanisms are still not fully understood. Here, we observed that motor dysfunction and dopaminergic neurons loss induced by rotenone exposure were ameliorated by cordycepin. Cordycepin also reversed Drp1-mediated aberrant mitochondrial fragmentation through increasing AMPK phosphorylation and maintained normal mitochondrial morphology. Additionally, cordycepin effectively increased adenosine 5'-triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reduced mitochondrial ROS levels, as well as inhibited complex 1 activity. More importantly, cordycepin administration inhibited the expression of NLRP3 inflammasome components and the release of pro-inflammatory cytokine in rotenone-induced rats and cultured neuronal PC12 cells. Moreover, we demonstrated that the activation of NLRP3 inflammasome within neurons could be suppressed by the mitochondrial division inhibitor (Mdivi-1). Collectively, the present study provides evidence that cordycepin exerts neuroprotective effects partially through preventing neural NLRP3 inflammasome activation induced by Drp1-dependent mitochondrial fragmentation in rotenone-injected PD models.


Assuntos
Anti-Inflamatórios/uso terapêutico , Desoxiadenosinas/uso terapêutico , Dinaminas/antagonistas & inibidores , Dinâmica Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Rotenona/toxicidade , Animais , Anti-Inflamatórios/farmacologia , Desoxiadenosinas/farmacologia , Relação Dose-Resposta a Droga , Dinaminas/metabolismo , Inseticidas/toxicidade , Masculino , Dinâmica Mitocondrial/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Células PC12 , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Ratos , Ratos Sprague-Dawley
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