Prenatal stress: long-term effects on the behavior and tryptophan metabolites balance by kynurenine pathway
Prenatal stress, psychiatric disorders, kynurenine, quinolinic acid, kynurenic acid, animal model.
Prenatal stress (PS) directly interferes on fetal programming, a principle in which the mother's endocrine and metabolic environment can result in long-term consequences for the adult offspring, including learning deficits, anxiety disorders, depression, autism, and schizophrenia. Among the PS neurochemical modifications in the fetal brain, is highlighted the kynurenine pathway, the main route of tryptophan metabolism, resulting in neuroactive metabolites. Our study aims to investigate the behavioral and neurochemical consequences of prenatal stress, with special focus on the kynurenine pathway metabolites balance, using adult offspring of mice. In the first stage of this study, Swiss mice pregnant females were submitted to restraint stress associated with bright light three times for day during the last week of gestation (E 14-21). Behavioral tests were conduct in both sexes of adult offspring (2 months), including: object recognition task, elevated plus maze, open field, social interaction, rota-rod, and tail suspension test. Another part of the adult offspring that were not used for behavioral tests had their brains and blood collected for further biochemical analysis. The second stage of this study will involve neurochemical tests to evaluate kynurenine pathway metabolites, including quantitative PCR, western blot and quantification of metabolites by HPLC - mass spectrometry. For this propose, the EPN protocol will be repeated in order to increase the sample. The first stage of this study revealed that the adult offspring submitted to prenatal stress presented: (1) mnemonic deficit in the object recognition task in male and female offspring, (2) anxious-like behavior in the elevated plus maze in the male offspring, (3) anxiolytic-like behavior in the elevated plus maze in the female offspring, (4) lower social interaction in the female offspring. In conclusion, the EPN model used in this study resulted in a gender-dependent behavioral alteration in the adult offspring of mice, suggesting to an associated profile in the literature with anxiety disorders in male offspring and autism and schizophrenia disorders in the female offspring. It is expected in the second step, to relate the behavioral results with the neurochemical balance, accessed by molecular analyzes.