Occupational-like organophosphate exposure disrupts microglia and accelerates deficits in a rat model of Alzheimer’s disease

Jaymie R. Voorhees, Matthew T. Remy, Claire M. Erickson, Laura M. Dutca, Daniel J. Brat, Andrew A. Pieper*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3
Journalnpj Aging and Mechanisms of Disease
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2019

Funding

We thank Dr. Robert Cohen for generously providing a male TgF344-AD hemizygous breeder to our laboratory for establishment of the animal colony. This work was supported by the National Institute for Environmental Health Sciences through the University of Iowa Environmental Health Sciences Research Center (NIEHS/NIH P30 ES005605) to J.R.V. and A.A.P., funds to A.A.P. from the Brockman Medical Research Foundation, funds to A.A.P. from an anonymous donor to the Mary Alice Smith Fund for Neuropsychiatry Research, funds to A.A.P. from the Titan Neurology Research Fund, Department of Veterans Affairs Merit Review 1IO1BX002444 to A.A.P., and CDA number IK2 RX002003 from USA Department of Veterans Affairs RR&D to L.M.D. The contents of this manuscript do not represent the views of the USA Department of Veterans Affairs or the USA Government.

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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