Aprendizagem e memória em ratos submetidos ao tratamento com extrato padronizado de Ginkgo biloba (EGb 761): Identificação de eventos moleculares
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Data
2009-01-28
Autores
Oliveira, Daniela Rodrigues de [UNIFESP]
Orientadores
Cerutti, Janete Maria [UNIFESP]
Tipo
Dissertação de mestrado
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Resumo
Embora os dados na literatura sugiram um efeito benéfico do extrato padronizado de Ginkgo biloba (EGb 761) na memória, os dados comportamentais bem como as modificações celulares e moleculares ainda são insuficientes para suportar tais indicativas. Neste sentido, o presente estudo avaliou o efeito do tratamento agudo (1 dia), subagudo (uma dose diária/7 dias) e crônico (uma dose diária/29 dias) com EGb 761 nas doses de 0,5 g.Kg-1 e 1,0 g.Kg-1 em ratos submetidos ao teste da resposta emocional condicionada (R.E.C.) em comparação com grupo controle positivo (Diazepam 4 mg.Kg-1) e negativo (Tween 80 – 12%). Para este estudo foram utilizados ratos Wistar (± 250 - 300 g), machos, adultos distribuídos em grupos de acordo com o tratamento e dose utilizados. Os dados mostram que os ratos submetidos ao diferentes tratamentos apresentaram aquisição do medo condicionado. Adicionalmente, nós investigamos a expressão de genes CREB-1 e GAP-43, associados ao medo condionado, além do gene canditado GFAP, em amostras do córtex pré-frontal, amígdala e hipocampo de ratos submetidos ao tratamento e a REC. O mRNA CREB-1, GAP-43 e GFAP e a expressão das proteínas foram avaliados utilizando as técnicas de PCR quantitativa (qPCR) e imunohistoquímica, respectivamente. Os dados mostram, pela primeira vez que o EGb 761 modula a expressão do CREB-1, GAP-43 e GFAP nas estruturas avaliadas. Nós observamos uma redução na expressão de GAP-43 em todas as estruturas avaliadas e um aumento de expressão de GFAP na amígdala e no hipocampo após o tratamento agudo com EGb 761 quando comparado com o grupo Tween (p<0.01). A expressão de GAP-43 foi diminuída no córtex pré-frontal e no hipocampo nos tratamentos subagudo e crônico com EGb 761. O tratamento subagudo com EGb 761 resultou na diminuição da expressão do CREB-1 no mPFC (p<0.001) e um aumento no hipocampo para o grupo EGb 761 na dose de 1,0 g. kg-1 (p<0.001). Adicionalmente, mostramos que o tratamento crônico com EGb 761 aumentou a expressão de GAP-43 na amígdala (p<0.01) e de CREB-1 na amígdala e hipocampo (p<0.001). Os resultados obtidos na análise imunohistoquímica suportam nossos achados e revelam que mudanças na expressão, ocorrem em regiões específicas nas regiões avaliadas. Os dados são importantes à medida que apresentam novas evidências para o papel do EGb 761 na memória, além de identificar
Although it has been suggested that the standardized Ginkgo biloba leaf extract (EGb 761) may have a benefic effect on memory, the cellular and molecular changes that underlie this process are not yet well defined. The present study evaluated the effects of acute (one dose), subacute (one daily dose/seven days) or chronic (one daily dose/twenty nine days) treatments with EGb 761 (0.5 g Kg-1 and 1.0 g Kg-1) on rats submitted to a conditioned emotional response (CER) in comparasion with positive (4 mg Kg-1Diazepam) and negative (12%Tween 80) control groups. To this end, adult, male, Wistar rats (± 250 - 300 g) were used in an off-baseline CER procedure (n=10/group). We here observed that the rats submitted to an acute, subacute and chronic EGb 761 treatment had acquisition of fear conditioning. Additionally, we investigate if the expression of genes previously associated with classical conditioning (CREB-1 and GAP-43) and candidate genes (GFAP) are modulated following EGb 761 acute, subacute and chronic treatments. CREB-1, GAP-43 and GFAP mRNA and protein expressions were evaluated using both quantitative PCR (qPCR) and immunohistochemical analysis, respectively. We here show, for the first time that EGb 761 modulated CREB-1, GAP-43 and GFAP expressions in the prefrontal cortex, amygdala and hippocampus. We observed an underexpression of GAP-43 in all structures evaluated and overexpression of GFAP in the amygdala and hipoccampus following acute Ginkgo biloba treatment when compared to control group (Tween; p<0.01). GAP-43 expression was decreased in prefrontal cortex and hippocampus in the subacute and chronic treatments with EGb 761. Subacute treatment with EGb 761 lead to a decreased to CREB-1 in mPFC (p<0.001) and overexpressed in the hippocampus to 1.0 g Kg-1 Ginkgo biloba group (p<0.001).Chronic treatment with EGb 761 lead to increased to GAP-43 in amygdala (p<0.01). Additiomally, we showed, that CREB-1 expression was increased in the amygdala and hippocampus in the chronic treatment with EGb 761(p<0.001).The results obtained from immunohistochemical analysis support our aforementioned findings and revelead that the changes in expression occurred within specific regions in the areas evaluated. All together, our findings not only provide new evidences for a role of EGb 761 on memory but also identify molecular changes that underlie the fear memory consolidation.
Although it has been suggested that the standardized Ginkgo biloba leaf extract (EGb 761) may have a benefic effect on memory, the cellular and molecular changes that underlie this process are not yet well defined. The present study evaluated the effects of acute (one dose), subacute (one daily dose/seven days) or chronic (one daily dose/twenty nine days) treatments with EGb 761 (0.5 g Kg-1 and 1.0 g Kg-1) on rats submitted to a conditioned emotional response (CER) in comparasion with positive (4 mg Kg-1Diazepam) and negative (12%Tween 80) control groups. To this end, adult, male, Wistar rats (± 250 - 300 g) were used in an off-baseline CER procedure (n=10/group). We here observed that the rats submitted to an acute, subacute and chronic EGb 761 treatment had acquisition of fear conditioning. Additionally, we investigate if the expression of genes previously associated with classical conditioning (CREB-1 and GAP-43) and candidate genes (GFAP) are modulated following EGb 761 acute, subacute and chronic treatments. CREB-1, GAP-43 and GFAP mRNA and protein expressions were evaluated using both quantitative PCR (qPCR) and immunohistochemical analysis, respectively. We here show, for the first time that EGb 761 modulated CREB-1, GAP-43 and GFAP expressions in the prefrontal cortex, amygdala and hippocampus. We observed an underexpression of GAP-43 in all structures evaluated and overexpression of GFAP in the amygdala and hipoccampus following acute Ginkgo biloba treatment when compared to control group (Tween; p<0.01). GAP-43 expression was decreased in prefrontal cortex and hippocampus in the subacute and chronic treatments with EGb 761. Subacute treatment with EGb 761 lead to a decreased to CREB-1 in mPFC (p<0.001) and overexpressed in the hippocampus to 1.0 g Kg-1 Ginkgo biloba group (p<0.001).Chronic treatment with EGb 761 lead to increased to GAP-43 in amygdala (p<0.01). Additiomally, we showed, that CREB-1 expression was increased in the amygdala and hippocampus in the chronic treatment with EGb 761(p<0.001).The results obtained from immunohistochemical analysis support our aforementioned findings and revelead that the changes in expression occurred within specific regions in the areas evaluated. All together, our findings not only provide new evidences for a role of EGb 761 on memory but also identify molecular changes that underlie the fear memory consolidation.
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Citação
OLIVEIRA, Daniela Rodrigues de. Aprendizagem e memória em ratos submetidos ao tratamento com extrato padronizado de Ginkgo biloba (EGb 761): Identificação de eventos moleculares. 2009. 162 f. Dissertação (Mestrado) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.