Long-term effects of early exposure to chlorpyrifos on the cholinergic pathway in transgenic apoe4 mice

Identifier:  TFG:1635

Handle: https://hdl.handle.net/20.500.11797/TFG1635

Authors:  Cruz Cobo, María

Abstract:
Chlorpyrifos (CPF) is one of the most used organophosphate pesticides in the world. Its action is based on the inhibition of acetylcholinesterase (AChE), which results in a cholinergic syndrome and subsequently the death of the insect. The exposure to this insecticide has been linked to numerous pathologies, such as Alzheimer’s disease (AD). AD is the most common senile dementia in the world, whose major risk factors are age and the Ɛ4 allele of apolipoprotein E (APOE4). The genotype apoE4 is associated with deficits in the compensation of the cholinergic system in the hippocampus, one of the most affected brain areas in AD patients. Damage to the hippocampus and a decrease in the activity of the cholinergic system are associated with cognitive impairment (characteristic of AD), developing problems related to learning and spatial memory. The aim of this study is to study the long-term effects of early exposure to CPF in male and female mice, as well as to determine the influence of the apoE4. For this purpose, the expression of 9 cholinergic genes was evaluated in the hippocampus of 9-month-old mice after postnatal exposure to CPF. The results obtained corroborated previous studies, exposing a difference between males and females. This study shows significant differences in the apoE4 individuals, suggesting basal alterations in the cholinergic system, linked to this genotype. Also, the effect of the CPF differs significantly between both genotypes and both sexes.