Oliveira Daniela R, Sanada Priscila F, Saragossa Filho A C, Innocenti L R, Oler Gisele, Cerutti Janete M, Cerutti Suzete M
Department of Biological Science, Federal University of Sao Paulo, SP, Brazil.
Brain Res. 2009 May 7;1269:68-89. doi: 10.1016/j.brainres.2008.11.105. Epub 2008 Dec 29.
Although it has been suggested that the standardized Ginkgo biloba leaf extract (Egb 761) may have a beneficial 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) or subacute treatments (one daily dose/seven days) with EGb 761 (0.5 g kg(-1) and 1.0 g kg(-1)) on rats submitted to a conditioned emotional response (CER) in comparison with positive (4 mg kg(-1) Diazepam) and negative (12%Tween 80) control groups. To this end, eighty (n=10/group) adult, male, Wistar rats (+/-250-300 g) were used in an off-baseline CER procedure. We here observed that the rats submitted to an acute and subacute EGb 761 treatments had acquisition of fear conditioning. Additionally, we investigate if the expression of genes previously associated with classical conditioning (CREB-1 and GAP-43) and new candidate genes (GFAP) are modulated following EGb 761 acute treatment. 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 GAP-43, CREB-1 and GFAP expression in the prefrontal cortex, amygdala and hippocampus. We observed an underexpression of GAP-43 in all structures evaluated and over-expression of GFAP in the amygdala and hippocampus following acute G. biloba treatment when compared to control group (Tween; p<0.01). GAP-43 expression was decreased in prefrontal cortex and hippocampus in the subacute treatment with EGb 761. Subacute treatment with EGb 761 lead to a decreased CREB-1 in mPFC (p<0.001) and increased in the hippocampus to 1.0 g kg(-1)G. biloba group (p<0.001). The results obtained from immunohistochemical analysis support our aforementioned findings and revealed that the changes in expression occurred within specific regions in the areas evaluated. All together, our findings not only provide new evidence for a role of EGb 761 on memory but also identify molecular changes that underlie the fear memory consolidation.
尽管有研究表明标准化银杏叶提取物（Egb 761）可能对记忆有有益影响，但这一过程背后的细胞和分子变化尚未明确界定。本研究评估了Egb 761（0.5 g kg(-1)和1.0 g kg(-1)）急性（一剂）或亚急性治疗（每日一剂/七天）对接受条件性情绪反应（CER）的大鼠的影响，并与阳性（4 mg kg(-1)地西泮）和阴性（12%吐温80）对照组进行比较。为此，八十只（n = 10/组）成年雄性Wistar大鼠（±250 - 300 g）用于非基线CER实验。我们在此观察到，接受急性和亚急性Egb 761治疗的大鼠获得了恐惧条件反射。此外，我们研究了在Egb 761急性治疗后，先前与经典条件反射相关的基因（CREB - 1和GAP - 43）以及新的候选基因（GFAP）的表达是否受到调节。分别使用定量PCR（qPCR）和免疫组织化学分析评估CREB - 1、GAP - 43和GFAP的mRNA和蛋白表达。我们首次在此表明，Egb 761调节了前额叶皮质、杏仁核和海马体中GAP - 43、CREB - 1和GFAP的表达。与对照组（吐温；p < 0.01）相比，我们观察到在急性银杏叶治疗后，所有评估结构中GAP - 43表达下调，杏仁核和海马体中GFAP表达上调。在Egb 761亚急性治疗中，前额叶皮质和海马体中GAP - 43表达降低。Egb 761亚急性治疗导致内侧前额叶皮质中CREB - 1降低（p < 0.001），在海马体中1.0 g kg(-1)银杏叶组中CREB - 1升高（p < 0.001）。免疫组织化学分析结果支持了我们上述发现，并揭示了在所评估区域的特定区域内发生了表达变化。总之，我们的研究结果不仅为Egb 761在记忆方面的作用提供了新证据，还确定了恐惧记忆巩固背后的分子变化。
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