Ectopic expression of α-synuclein affects the migration of neural stem cells in mouse subventricular zone

P>alpha-Synuclein (alpha-syn) is a key protein in Parkinson's disease (PD), and its abnormal accumulation is implicated only not in the loss of dopaminergic neurons in the substantia nigra but also in impairment of olfactory bulb (OB) in PD. Olfactory dysfunction could arise from these OB changes as an early symptom in PD. We reported previously the impairment of neuronal stem cell (NSC) proliferation in the subventricular zone, which is upstream of OB in PD models. Reduction of NSC generation could potentially lead to olfactory dysfunction, which is commonly associated with and precedes the motor symptoms by several years in PD. Here, we investigated neurosphere formation in vitro and migration of NSCs in vivo after transduction of alpha-syn-encoding retroviral vector to characterize the function of alpha-syn in NSC. Over-expression of alpha-syn caused less effective formation of neurospheres and induced morphological changes. Fluorescence-activated cell sorting showed diminished NSC cell cycle progression induced by over-expression of alpha-syn. Intriguingly, suppression of NSC migration along the rostral migratory stream was observed when the alpha-syn-encoding vector was directly injected into the subventricular zone of mice in vivo. These results indicate that alpha-syn affects the generation of NSC and suggest that this protein could serve as a tool for the design of potentially useful therapy for PD patients.