Efeitos da privação de sono paradoxal na expressão de receptores para corticosteróides no hipocampo, de moléculas envolvidas na modulação do sono e no aprendizado e memória de ratos submetidos a modelo de hipóxia isquemia pré-natal

Abstract

The decrease of oxygen during gestation, prenatal hypoxia-ischemia (HI), can generate damages in youth and adult life such as hyperactivity, impaired concentration and learning, memory deficit, sleep disturbances, pain and in more severe cases epilepsy and cerebral palsy. Glucocorticoid receptors (GcR) and mineralocorticoid receptors (MnR) are largely co-expressed in hippocampal neurons and the balance of their actions is essential for the activity of these neurons. Hypoxia is known to increase GcR which is related to cell death and to decrease MnR level, related to cell survival. Hypobaric hypoxia models have already shown damages in hippocampal neurons in CA1 and CA3 regions as well as increased oxidative stress and antioxidant responses in the cerebellum and brainstem. Furthermore the hypobaric hypoxia changes the architecture of sleep and alters the levels of biomolecules involved in the regulation of sleep and wakefulness. Paradoxical sleep deprivation (PSD) during hypobaric hypoxia induces an increase in antioxidative response. The objective of this study was to evaluate the morphological and functional effects of PSD in adulthood in a prenatal systemic HI model. We evaluated the levels of GAD enzyme; the distribution of corticosteroid receptors; learning and memory and the interaction between PSD and HI. Rats on the 18th day of gestation had the four uterine arteries blocked for 45 minutes (HI). Control animals had wombs exposed without the obstruction (SH). The pregnancy continued and only pups born at term were used. At 90 postnatal days, the groups were divided and half of them submitted to PSD through the multiple platforms water tank. GAD was analised by western blotting technique. The test of passive avoidance for evaluation of learning and memory was used. After the test the animals were euthanized and their brains histologically reacted with anti-GcR and anti-MnR antibodies. Our results showed an increase in the level of the GAD enzyme in the locus coeruleus (LC) and in the hippocampus in the HI group compared to the SH group. After PSD, the levels of GAD enzyme in HI group showed a significant reduction when compared to the HI control group only in the LC. In the evaluation of corticosteroid receptors, there were no significant differences between HI and SH groups. After PSD the HI group showed an increase in GcR staining intensity in the hippocampal dentate gyrus (DG). There were no significant differences in learning and memory between SH and HI groups, even after PSD. We can conclude that there was a change in the enzyme that synthesizes one of the neurotransmitters involved in the modulation of sleep with a possible reversal of the changes after PSD. Concerning GcR/MnR, HI was not able to alter the balance between corticosteroid receptors in the hippocampal region, with the only change been obsereved in DG receptors after PSD. Despite the neurochemical changes in the hippocampus, there were no changes in learning and memory.