Nicotine Amelioratesα-synuclein Pre-formed Fibril-Induced Behavioral Deficits and Pathological Features in Mice

Background Epidemiologic study suggests nicotine reduces risk of PD, could be potential treatment for Parkinson’s disease. Objective To study the effect of nicotine on behavioral phenotypes and pathological characteristics of mice induced by human alpha-synuclein preformed fibers (α-syn-PFF). Methods Mice were injected with 5 μg of human α-syn-PFF in the hippocampus while administering nicotine-containing drinking water (200μg/mL). After 1 month, the motor ability, mood, spatial learning, and memory ability of the Parkinson’s disease(PD)phenotype-like model were detected using open field, rotarod, Y maze, and O maze tests. The expression of pathological α-syn, apoptotic proteins and the numbers of glial cells and neural stem cells in the hippocampus of mice were detected using western blotting and immunofluorescence. Results Nicotine significantly reduced pathological α-syn accumulation, α-syn serine 129 phosphorylation and cell death caused by PFF injection in the hippocampus of mice, inhibited the increase of glial, microglia and apoptotic cells, decreased the expression levels of PI3K and Akt. Conclusions Nicotine may have inhibitory effects on human α-syn-PFF-induced neuroinflammation and apoptosis. Thus, it reduces human α-syn-PFF-induced behavioral deficits and pathological changes in mice.