Benzo(A)Pyrene Exposure In Utero Exacerbates Parkinson'S Disease (Pd)-Like Alpha-Synucleinopathy In A53t Human Alpha-Synuclein Transgenic Mice

Background: Previous work indicated that benzo [al pyrene (B(alpha)P) exposure in utem might adversely affect neurodevelopment and cause Parkinson's Disease (PD)-like symptoms. However, the effect of utero exposure to B (alpha)P on PD-like alpha-synucleinopathy and the mechanism under are unclear.Objective: The A53T human alpha-synuclein (alpha-syn) transgenic mice (M83(+/-)) were used in this study to gain insights into the role of B(alpha)P exposure in utero in the onset of alpha-syn pathology and neuronal damage.Method: Timed-pregnant M83(+/-) dams were exposed to 1) corn oil (vehicle) or 2) 5 mg/kg bw/d B(alpha)P or 3) 20 mg/kg bw/d B(alpha)P at gestational day 10-17 by oral gavage and then the SNCA transcription, alpha-syn accumulation and aggregation, neuroinflammation and nigral dopaminergic neumdegeneration of 60-day-old pups were evaluated.Result: SNCA mRNA and alpha-syn protein expression in the midbrain of 60 days adult mice were found to be remarkably elevated after B(alpha)P exposure in utero, the protein degradation capacity was injured (in 20 mg/kg dose group) and alpha-syn aggregation could be observed in the substantia nigra (SN); Enhanced Iba1 expression in the midbrain and microglial activation (in 20 mg/kg dose group) in the SN were also figured out; Besides, dopaminergic neurons in the SN of 60 days adult mice were significantly decreased.Conclusions: Our findings demonstrated that B(alpha)P exposure in utero could exacerbate alpha-syn pathology and induce activation of microglia which might further lead to dopaminergic neuronal loss in the SN.