Tracking ClODynamics during the Progression of Parkinson's Disease in MPTP Mouse Model UsingBrain Microdialysis.

Abstract

Oxidative stress induced by hypochlorite (ClO) is significant in Parkinson's disease (PD) pathogenesis, yet the dynamic variation in the brain's ClOlevel during PD progression remains unclear. Herein, we developed a new reliable method combiningmicrodialysis brain sampling with fluorescence detection for accurate and real-time tracking of local ClOlevels in the striatum. In the strategy, N,P--doped fluorescent carbon dots (N,P-CDs) with a high positive charge (22.33 mV) and an average particle size (4.4 nm) were synthesized, exhibiting membrane-impermeability, fast response, high selectivity, and good sensitivity toward ClO. Leveraging the electrostatic attraction between N,P-CDsand ClO, an N,P-CDs-functionalized microdialysis perfusate for rapid capture of ClOwas constructed, yielding a 6.13-fold enhancement in the microdialysis recovery compared with artificial cerebrospinal fluid (aCSF). Importantly, this is the first report of a sustained elevation of the ClOlevel in the striatum of MPTP-induced acute PD model mice for up to 11 h, accompanied by increased expression of the microglia-specific protein IBA1 and the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Overall, this work provides a powerful analytical method fordetection of ClO, and simultaneously reveals the variation pattern of the ClOlevel in PD pathogenesis.