期刊
NPJ AGING AND MECHANISMS OF DISEASE
卷 5, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41514-018-0033-3
关键词
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资金
- National Institute for Environmental Health Sciences through the University of Iowa Environmental Health Sciences Research Center [NIEHS/NIH P30 ES005605]
- Brockman Medical Research Foundation
- Titan Neurology Research Fund, Department of Veterans Affairs Merit Review [1IO1BX002444]
- USA Department of Veterans Affairs RR D [IK2 RX002003]
Occupational exposure to organophosphate pesticides, such as chlorpyrifos (CPF), increases the risk of Alzheimer's disease (AD), though the mechanism is unclear. To investigate this, we subjected 4-month-old male and female wild-type (WT) and TgF344-AD rats, a transgenic AD model, to an occupational CPF exposure paradigm that recapitulates biomarkers and behavioral impairments experienced by agricultural workers. Subsequent cognition and neuropathology were analyzed over the next 20 months. CPF exposure caused chronic microglial dysregulation and accelerated neurodegeneration in both males and females. The effect on neurodegeneration was more severe in males, and was also associated with accelerated cognitive impairment. Females did not exhibit accelerated cognitive impairment after CPF exposure, and amyloid deposition and tauopathy were unchanged in both males and females. Microglial dysregulation may mediate the increased risk of AD associated with occupational organophosphate exposure, and future therapies to preserve or restore normal microglia might help prevent AD in genetically vulnerable individuals exposed to CPF or other disease-accelerating environmental agents.
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