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Occupational-like organophosphate exposure disrupts microglia and accelerates deficits in a rat model of Alzheimer's disease.
Voorhees, Jaymie R; Remy, Matthew T; Erickson, Claire M; Dutca, Laura M; Brat, Daniel J; Pieper, Andrew A.
Afiliación
  • Voorhees JR; 1Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA USA.
  • Remy MT; 2Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Graduate College, Iowa City, IA USA.
  • Erickson CM; 1Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA USA.
  • Dutca LM; 1Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA USA.
  • Brat DJ; 3The Iowa City Department of Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States Departments of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA USA.
  • Pieper AA; 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL USA.
NPJ Aging Mech Dis ; 5: 3, 2019.
Article en En | MEDLINE | ID: mdl-30701080
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.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Aging Mech Dis Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Aging Mech Dis Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido