Influencia del genotipo apoE en la expresión de efectos neuroconductuales derivados de la exposición postnatal a clorpirifós

Identifier:  TDX:2569

Handle: https://hdl.handle.net/20.500.11797/TDX2569

Authors:  Basaure García, Pia Isabel

Abstract:
Chlorpyrifos (CPF) is one of the most used pesticides in the world. Several research studies have evidenced that CPF exposure in low doses cause detrimental effects in children and adults. At the same time, the two most frequent isoforms of human apolipoprotein E (apoE) have demonstrated to affect differentially neurobiological and metabolic processes. It is well known that the apoE genotype presents specific interactions with environmental factors. The principal aim of this thesis was to study the influence of the apoE genotype in physical, behavioral and biochemical changes due to a postnatal exposure to CPF in a short-, intermediate- and long-term, also evaluating the response of a re-exposure in adults. Transgenic male and female mice homozygous for the human ε3 or ε4 alleles of the APOE human gene were used for this study, being exposed at doses of 0 or 1 mg/kg/day of CPF from postnatal day 10 to 15, and a re-exposure at doses of 0 or 2 mg/kg/day from the fifth and seventh month, carrying it out different assessments during those seven months. Overall, apoE3 and apoE4 mice showed differences in all the levels studied since their birth. The postnatal CPF exposure modified the gene expression of determined liver markers and from the cholinergic system of brain at short-term; the social behavior in apoE3 mice and learning performance in apoE4 female mice both at long-term; and it also triggered several changes over the body weight in male of both genotypes starting at the third month. CPF exposure in adulthood affected glycaemia, learning and memory and cholinesterase brain activity in apoE4 mice, according to sex type. Taken together, these findings demonstrated that CPF manifests its effects depending on the apoE genotype, age and sex, providing new insights about the vulnerability present in each subpopulation to this pesticide.