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Study of neuroinflammation markers in the hippocampus of adolescent rats after binge-like ethanol exposure
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O início do consumo de álcool ocorre tipicamente durante a adolescência e os modos de consumo produzem efeitos visíveis a nível social e de saúde. A adolescência é um período de vida durante o qual ocorrem importantes processos do desenvolvimento cerebral, tendo sido previamente demonstrado que o cérebro adolescente é mais susceptível ao comprometimento da memória e danos cerebrais induzidos pelo etanol, pelo que o consumo excessivo de álcool pode gerar níveis neurotóxicos de intoxicação e ao desenvolvimento de efeitos profundos no sistema nervoso central.
Estudos previamente realizados no laboratório GRAP demonstraram que uma exposição ao álcool do tipo binge-drinking através da administração de duas injecções consecutivas de etanol (3g/kg i.p.) em ratos foi suficiente para originar a abolição da plasticidade sináptica na região CA1 do hipocampo, bem como perdas nas habilidades de aprendizagem. Dada a relação recentemente descoberta entre a plasticidade sináptica e neuroinflamação, pretende-se agora investigar se este protocolo de exposição do tipo binge-drinking será capaz de provocar eventos neuroinflamatórios nas subregiões CA1 e Dentate Gyrus do hipocampo, utilizando dois marcadores de neuroinflamação, HMGB1 (High-mobility group box 1 protein) e TLR4 (Toll-like receptor).
Os resultados do protocolo de imunohistoquímica realizado para HMGB1 revelaram que não existe diferenças estatisticamente significativas da expressão de HMGB1 entre o grupo de ratos submetidos à exposição do tipo binge-drinking e o grupo de controlo, o que sugere que a exposição excessiva ao etanol não altera a expressão de HMGB1, nem induz a ocorrência de fenómenos inflamatórios nas células neuronais, em nenhuma das subregiões do hipocampo em estudo. O estudo de imunofluorescência realizado revelou a ocorrência de um aumento da expressão de TLR4 nas duas subregiões do hipocampo em estudo dos ratos sujeitos à administração de álcool. Estes resultados sugerem que este protocolo do tipo binge-drinking parece ser suficiente para induzir fenómenos de neuroinflamação no hipocampo dos ratos.
The initiation of alcohol consumption typically occurs during adolescence and the patterns of drinking have an effect on health and social outcomes. The adolescence is a period of life, during which strong processes of brain development take place, having been previously demonstrated that adolescent brain is more susceptible to ethanol-induced memory impairment or brain damage, whereby excessive alcohol consumption may drive to neurotoxic levels of intoxication and to the development of profound effects on the central nervous system. Previous studies performed in GRAP laboratory demonstrated that binge-like ethanol exposure with two close injections of ethanol (3g/kg i.p.) in rat was enough to produce synaptic plasticity abolition in the CA1 of hippocampus, together with losses in learning abilities. Given the recently discovered relation between synaptic plasticity and neuroinflammation, we intended in this work to investigate whether this binge-like exposure protocol would be able to produce neuroinflammatory events in the CA1 field and Dentate Gyrus of the hippocampus, using two neuroinflammation markers, HMGB1 (High-mobility group box 1 protein) and TLR4 (Toll-like receptor). The results of the immunohistochemistry experiment performed for HMGB1 revealed that there are no statistically significant differences between the HMGB1 expression in group of rats exposed to the binge-drinking and the control group, which suggest that the binge-like ethanol exposure doesn't alter the HMGB1 expression and it doesn’t induce inflammatory phenomena in neurons, neither in CA1 nor Dentate Gyrus. The immunofluorescent study performed revealed an increase of TLR4 expression in both hippocampus subregions of binged rats, which suggests that this binge-like ethanol exposure protocol seems to be sufficient to induce neuroinflammation in the hippocampus of rats.
The initiation of alcohol consumption typically occurs during adolescence and the patterns of drinking have an effect on health and social outcomes. The adolescence is a period of life, during which strong processes of brain development take place, having been previously demonstrated that adolescent brain is more susceptible to ethanol-induced memory impairment or brain damage, whereby excessive alcohol consumption may drive to neurotoxic levels of intoxication and to the development of profound effects on the central nervous system. Previous studies performed in GRAP laboratory demonstrated that binge-like ethanol exposure with two close injections of ethanol (3g/kg i.p.) in rat was enough to produce synaptic plasticity abolition in the CA1 of hippocampus, together with losses in learning abilities. Given the recently discovered relation between synaptic plasticity and neuroinflammation, we intended in this work to investigate whether this binge-like exposure protocol would be able to produce neuroinflammatory events in the CA1 field and Dentate Gyrus of the hippocampus, using two neuroinflammation markers, HMGB1 (High-mobility group box 1 protein) and TLR4 (Toll-like receptor). The results of the immunohistochemistry experiment performed for HMGB1 revealed that there are no statistically significant differences between the HMGB1 expression in group of rats exposed to the binge-drinking and the control group, which suggest that the binge-like ethanol exposure doesn't alter the HMGB1 expression and it doesn’t induce inflammatory phenomena in neurons, neither in CA1 nor Dentate Gyrus. The immunofluorescent study performed revealed an increase of TLR4 expression in both hippocampus subregions of binged rats, which suggests that this binge-like ethanol exposure protocol seems to be sufficient to induce neuroinflammation in the hippocampus of rats.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Palavras-chave
HMGB1 TLR4 Neuroinflammation Binge-drinking Alcohol Mestrado Integrado - 2017