Drp1, a potential therapeutic target for Parkinson’s disease, is involved in olfactory bulb pathological alteration in the Rotenone-induced rat model

• DOI: 10.1016/j.toxlet.2020.02.009
• Publication Date: 2020-02-20T21:56:56Z
• Authors: Xiaoling Zhang; Wenmin Huang; Qianhang Shao; Yuan Yang; Zhengxin Xu; Jing Chen; Xiaoyan Zhang; Xiaoqun Ge
• Keywords: Dynamins; Male; Neurons; 0301 basic medicine; Movement Disorders; Tyrosine 3-Monooxygenase; Inflammasomes; Uncoupling Agents; NF-kappa B; Nitric Oxide Synthase Type II; Olfactory Bulb; Mitochondria; Rats; Rats, Sprague-Dawley; Smell; 03 medical and health sciences; Rotenone; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Parkinson Disease, Secondary

Olfaction is often affected in parkinsonian patients and its disturbances precede the classical cognitive and locomotor dysfunction. The olfactory bulb might be the region of onset in Parkinson's disease (PD) pathogenesis, evidenced by the presence of disease-related protein aggregates and disturbed olfactory information processing. However, the underlying molecular mechanism that governs the olfactory bulb impairments remains unclear. This study was designed to investigate the relationship between olfactory bulb and inflammatory pathological alterations and the potential mechanisms. Here we found that rotenone led to typical parkinsonian symptoms and decreased tyrosine hydroxylase (TH)-positive neurons in the olfactory bulb. Additionally, increased NF-κB nuclear translocation and NLRP3 inflammasome components expressions caused by rotenone injection were observed accompanied by the activation of microglia and astrocytes in the olfactory bulb. Rotenone also triggered Drp1-mediated mitochondrial fission and this in turn caused mitochondrial damage. Furthermore, Mdivi-1(a selective Drp1 inhibitor) markedly ameliorated the morphologic disruptions of mitochondria and Drp1 translocation, inhibited the nuclear translocation of NF-κB, eventually blocked the downstream pathway of the NLRP3/caspase-1/IL-1β axis and expression of iNOS. Overall, these findings suggest that Drp1-dependent mitochondrial fission induces NF-κB nuclear translocation and NLRP3 inflammasome activation that may further contribute to olfactory bulb disturbances.