Efeitos de diferentes estratégias de neuroproteção na redução dos déficits de memória induzidos pelo estresse no início da vida

Abstract

During the neonatal period, stressful events influence the brain development, promoting learning and memory deficits that can persist into adulthood. Biochemical and morphological changes resulting from this type of stress, mimicked by maternal deprivation (MD), are associated with several psychosocial disorders such as depression and schizophrenia. Considering the deleterious effects of stress, we hypothesize that the use of neuroprotective strategies, such as acute aerobic exercise (AE), exposure to novelty, and peripheral administration of a dopamine precursor (LDopa) can modulate the memory consolidation and persistence in young adult rats submitted to MD. To test our hypothesis, we performed three different studies using the same MD model. In all three studies, we demonstrated that PM impairs memory consolidation and persistence. In the first study of this thesis, we investigated the effects of an AE session on object recognition (OR) memory consolidation and persistence. We demonstrate that acute exercise can modulate learning, promoting memory acquisition and persistence in MD rats for up to 21 days. However, despite the MD had altered the levels of dopamine (DA) and norepinephrine (NE) in the hippocampus of rats, the exercise did not modulate these parameters. In the second study we investigated the effects of a novelty exposure before the OR learning session on memory consolidation and persistence in MD rats. We show that exposure to novelty can modulate learning, promoting memory acquisition and persistence. Finally, the third study os this thesis we demonstrated that the stimulation of the dopaminergic system through the peripheral administration of L-Dopa before the OR learning, reverses the MD-related memory impairment, what, in association to another results, demonstrates the role of dopaminergic system in the physiopathology of MD. The set of results presented in this work confirms that MD causes cognitive deficits in rats and that accessible non-invasive neuroprotective strategy can act on these deficits. Although our behavioral results were enlightening, we believe that further studies should be carried out to elucidate the mechanisms of action involved in the observed effects.