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

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.

SUBMITTER: Voorhees JR

PROVIDER: S-EPMC6342990 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe aim of this study was to conduct a systematic review of the published literature and to estimate whether or not there is a causal relationship between occupational exposure to organophosphate pesticides (OPs) and either neurological impairment or depressive symptoms.Data sourcesEMBASE, MEDLINE, Global Health and PsycINFO (1980 to April 2014).SettingObservational studies (cross-sectional, cohort and case-control studies) with exposed and unexposed groups.ParticipantsPeople who occupationally use OPs for more than 1?month and their family.Primary outcomeResults of neurological core test batteries or depressive symptoms such as headaches, anxiety and dizziness.Study appraisal and synthesis methodsAfter an extensive search of various literature databases, one author screened titles and abstracts, searched the relevant publications manually and conducted data extraction. All extracted data from the selected articles were synthesised for analysis. Quality appraisal was conducted using the Newcastle Ottawa Scale.ResultsOf the 1024 articles retrieved by database search, 24 studies that met the inclusion and exclusion criteria were selected for analysis. Of the selected studies, 17 were cross-sectional and the remaining 7 were cohort and nested case-control studies. The geographical areas included in the studies were the USA (10 studies), the UK (4 studies), Africa (4 studies), Asia (3 studies), Europe (2 studies) and South America (1 study). Each of the included studies used different exposure and outcome assessments such as neurological scores and depressive symptoms, making it difficult to compare the results exactly. Most studies showed that exposed groups had poorer results than unexposed groups; however, owing to the inconsistent neurological test batteries, there was not enough pooling evidence to conduct a meta-analysis.ConclusionsThe findings of this literature review indicate that it is necessary to standardise the neurological or neuropsychological test battery and methods of measuring exposure to OPs.

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

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