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Published on: July 29, 2022
Benzo(a)pyrene exposure in utero exacerbates Parkinson's Disease (PD)-like α-synucleinopathy in A53T human
Weixing Xu1, Yuze Qi1, Yanjun Gao1
1Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China.
Insights
In utero exposure to benzo[a]pyrene (B(a)P) worsens alpha-synuclein (α-syn) pathology and causes neuroinflammation. This prenatal B(a)P exposure leads to dopaminergic neuron loss, suggesting a link to Parkinson's disease-like symptoms.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Prenatal exposure to benzo[a]pyrene (B(a)P) may negatively impact neurodevelopment and induce Parkinson's Disease (PD)-like symptoms.
- The specific effects of in utero B(a)P exposure on α-synucleinopathy and the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of in utero B(a)P exposure in the development of α-synuclein pathology and neuronal damage.
- To elucidate the mechanisms by which B(a)P affects the onset of PD-like symptoms in offspring.
Main Methods:
- Utilized A53T human alpha-synuclein (α-syn) transgenic mice (M83+/-).
- Timed-pregnant dams were exposed to B(a)P (5 or 20 mg/kg) or vehicle during gestational days 10-17 via oral gavage.
- Evaluated SNCA transcription, α-syn accumulation/aggregation, neuroinflammation, and dopaminergic neurodegeneration in 60-day-old pups.
Main Results:
- In utero B(a)P exposure significantly elevated SNCA mRNA and α-syn protein levels in adult offspring.
- Observed impaired protein degradation, α-syn aggregation in the substantia nigra (SN), and enhanced microglial activation (Iba1 expression).
- Significant decrease in dopaminergic neurons in the SN of B(a)P exposed offspring.
Conclusions:
- In utero B(a)P exposure exacerbates α-syn pathology and induces microglial activation.
- This neuroinflammation may contribute to dopaminergic neuronal loss in the substantia nigra.
- Findings suggest a potential link between prenatal B(a)P exposure and the pathogenesis of Parkinson's Disease.
Background:
Previous work indicated that benzo[a]pyrene (B(a)P) exposure in utero might adversely affect neurodevelopment and cause Parkinson's Disease (PD)-like symptoms. However, the effect of utero exposure to B(a)P on PD-like α-synucleinopathy and the mechanism under are unclear.
Objective:
The A53T human alpha-synuclein (α-syn) transgenic mice (M83+/-) were used in this study to gain insights into the role of B(a)P exposure in utero in the onset of α-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(a)P or 3) 20 mg/kg bw/d B(a)P at gestational day 10-17 by oral gavage and then the SNCA transcription, α-syn accumulation and aggregation, neuroinflammation and nigral dopaminergic neurodegeneration of 60-day-old pups were evaluated.
Result:
SNCA mRNA and α-syn protein expression in the midbrain of 60 days adult mice were found to be remarkably elevated after B(a)P exposure in utero, the protein degradation capacity was injured (in 20 mg/kg dose group) and α-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(a)P exposure in utero could exacerbate α-syn pathology and induce activation of microglia which might further lead to dopaminergic neuronal loss in the SN.
