Influence of prenatal chlorpyrifos exposure, APOE genotype and sex on neurodevelopmental disorders: behavioral and biochemical abnormalities in mice

Identificador:  TDX:4104

Handle: https://hdl.handle.net/20.500.11797/TDX4104

Autores:  Biosca Brull, Judit

Resumen:
The massive use of the pesticide chlorpyrifos (CPF) can trigger detrimental health effects, specially, in the developing population. In recent years, the increase in the diagnosis of autism spectrum disorder (ASD) has been associated with exposure to toxics. On the other hand, there are genetic polymorphism such as that of apolipoprotein E (APOE) that influence the response to environmental factors. In this thesis we have evalauted how prenatal exposure to CPF and the APOE genotype contribute to the behavioral and biochemical alterations observed in neurodevelopmental disorders. Females C57BL/6J and homozygous for the human e3 and e4 alleles were exposed trough the diet to 0 or 1 mg/kg/day of CPF from gestational day (GD) 12 to 18. In addition, a group of C57BL/6J females were exposed to 300 mg/kg/day of valproic acid (VPA) on GD 12 and 13, by a subcutaneous injection. Another group of C57BL/6J mice was orally exposed to 0 or 1 mg/kg/day of CPF from postnatal day 10 to 15. Dams of mice prenatally exposed were evaluated in maternal care and nest quality. Communication skills and physical and motor development were evalauted during lactation period, and anxiety behavior during adolescence, as well as the expression of elements involved in the GABAergic and glutamatergic system. Social behavior was assessed in adolescent mice exposed pre or postnatally to CPF. The effects induced in communication skills by prenatal CPF exposure were opposite to those observed with VPA in C57BL/6J mice, but both treatments delayed physical development, altered social behavior and changed the expression of some GABAergic and glutamatergic elements in a sex-dependent manner. Moreover, throughout the study, we observed differences between APOE genotype, except for social behavior, where both genotypes showed an affectation of the treatment depending on sex. In general, this thesis questions the association between CPF and ASD, and suggests that the different apoE isoforms (apoE3 and apoE4) are not a risk factor for the development of the disorder.