Alterações na modulação do GABA no hipocampo e redução de aprendizado e memória em ratos jovens submetidos à hipóxia-isquemia transitória pré-natal

• Autor(a) principal: Rodrigues, Marta Cristina da Cunha
• Data de Publicação: 2018
• Outros Autores: [e-mail]
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/18367
• topic: Prenatal lesion; Rats; Hippocampus; GAD; Neurodevelopment; Lesão pré-natal; Ratos; Hipocampo; GAD; Neurodesenvolvimento; CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA

Intrauterine adverse conditions may be responsible for long-lasting damages which impact health even during adult phase. Hypoxic-ischemic (HI) events are a relevant cause of newborn mortality and the principal factor leading to permanent brain lesions. Using a model in which the ovarian and uterine flux of a pregnant rat is obstructed for 45 minutes we have described oligodendrocyte death, astrogliosis and neuronal loss. In this work we investigated hippocampal neuronal population in relation to components of excitatory and inhibitory synapses and performed a functional evaluation of learning and memory of adolescent rats that had been affected by prenatal HI. Anesthetized Wistar rats on the 18th gestation day had the uterine horns exposed and the ovarian and uterine arteries clamped for 45 minutes (HI group). Sham-operated rats (SH group) had the horns exposed but no arteries were clamped. Histological evaluation was performed in order to characterize hippocampal neuronal population in adolescent rats. We also investigated the levels of proteins involved in glutamatergic and GABAergic transmission in the hippocampus, in its total fraction and in synaptic terminals. Synaptic plasticity phenomena in the hippocampus were also evaluated through electrophysiological records. The memory of rats from both groups was tested through novel and displaced object recognition tests as well as in Y-maze. It was possible to observe an increased parvalbumin immunostaining and increased levels of GAD enzyme in HI group although the total number of hippocampal neurons was decreased. Despite of the absence of alterations in LTP and depotentiation amplitude, behavioral assessment indicated a marked difference concerning HI learning and memory abilities. Males HI also displayed anxiety-like behavior in one of the tested conditions. Our results reflect permanent damages concerning GABA function which may disturb neurotransmitter homeostasis leading to the observed deficits in learning and memory.