Comportamento tipo depressivo em ratos submetidos a um modelo de hipóxia-isquemia pré-natal: avaliação morfofuncional

Abstract

Prenatal hypoxia-ischemia (HI) is a major cause of morbidity and mortality, with damage to the central nervous system (CNS). About 25% of babies diagnosed with HI encephalopathy develop long lasting sequelae, including depression, in the adulthood. Permanent lesions in the cerebral cortex post HI have been described and the prefrontal cortex (PFC) is a region related to mood modulation. The purpose of this study is to evaluate depressive behavior; the distribution of a proteic marker of synaptic activity (synaptophysin); neuronal population and the levels of tyrosine hydroxylase (TH) in the PFC of rats submitted to a model of prenatal HI. Wistar rats on the 18th day of gestation had their uterine horns exposed under anesthesia and their uterine arteries obstructed for 45min (Group HI). In the control group (SH), the uterine horns were also exposed, but without obstructing the arteries. After surgery, gestation continued and the pups were born at term. At the 45th postnatal day the offspring were submitted to the sucrose preference behavioral test and the forced swimming test, whose immobility is interpreted as depressive-like behavior. We observed that the HI group consumed less sucrose than the SH group. With the forced swim test we found that males from the HI group remained immobile longer than females from the same group and males from the HI group remained immobile longer than males from the SH group. We observed that the immunohistochemical labeling of synaptophysin was reduced in male animals that suffered hypoxic-ischemic insult when compared to males in the SH group. Furthermore, we observed a reduction in the number of neurons in the PFC of animals that suffered the injury. We also verified a reduction in TH enzyme levels in PFC of HI group male animals. Our data demonstrate that the HI insult in E18 significantly altered depressive-like behavior in HI male rats. In the same group, a reduction in synaptophysin labeling and TH enzyme levels in PFC was demonstrated. Our results reinforce the importance of this model in the study of the effects of injuries triggered by HI, as it reproduces the increase in depressive-like behavior in the HI group, and suggest that males are more vulnerable to changes triggered by HI in the circuitry related to mood modulation.