First Author | Xu W | Year | 2020 |
Journal | Biochem Biophys Res Commun | Volume | 533 |
Issue | 4 | Pages | 1148-1154 |
PubMed ID | 33046245 | Mgi Jnum | J:304660 |
Mgi Id | MGI:6693920 | Doi | 10.1016/j.bbrc.2020.09.101 |
Citation | Xu W, et al. (2020) Double-stranded RNA-induced dopaminergic neuronal loss in the substantia nigra in the presence of Mac1 receptor. Biochem Biophys Res Commun 533(4):1148-1154 |
abstractText | BACKGROUND: The underlying mechanism of viral infection as a risk factor for Parkinson's disease (PD), the second most common neurodegenerative disease, remains unclear. OBJECTIVE: We used Mac-1(-/-) and gp91(phox-/-) transgene animal models to investigate the mechanisms by which poly I:C, a mimic of virus double-stranded RNA, induces PD neurodegeneration. METHOD: Poly I:C was stereotaxically injected into the substantia nigra (SN) of wild-type (WT), Mac-1-knockout (Mac-1(-/-)) and gp91 (phox)-knockout (gp91 (phox-/-)) mice (10 mug/mul), and nigral dopaminergic neurodegeneration, alpha-synuclein accumulation and neuroinflammation were evaluated. RESULT: Dopaminergic neurons in the nigra and striatum were markedly reduced in WT mice after administration of poly I:C together with abundant microglial activation in the SN, and the expression of alpha-synuclein was also elevated. However, these pathological changes were greatly dampened in Mac-1(-/-) and gp91 (phox-/-) mice. CONCLUSIONS: Our findings demonstrated that viral infection could result in the activation of microglia as well as NADPH oxidase, which may lead to neuron loss and the development of Parkinson's-like symptoms. Mac-1 is a key receptor during this process. |