Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain-Shams University, Monazamet Al-Wehdah Al-Efrikeya St., Abbassia, Cairo 11566, Egypt.
Neurochem Int. 2011 Nov;59(6):770-8. doi: 10.1016/j.neuint.2011.07.012. Epub 2011 Jul 31.
3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington's disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions. Rats administered 3-NP (20mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity. Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects.
3-硝基丙酸（3-NP）是琥珀酸脱氢酶（SDH）的不可逆抑制剂，可诱导类似于亨廷顿病（HD）的神经退行性变。听觉惊跳反应的预脉冲抑制（PPI）降低、运动活动减少、双侧纹状体损伤以及大脑氧化应激是 HD 的主要特征。本研究旨在研究银杏叶提取物（EGb 761）对 3-NP 诱导的神经行为变化和纹状体损伤的神经保护作用。连续 5 天给予 3-NP（20mg/kg，sc）的大鼠表现出 PPI 缺陷和运动活动减少，而在 3-NP（20mg/kg，连续 5 天，从第 8 天开始）诱导 HD 之前和期间，用 EGb 761（100mg/kg，ip）预处理动物可改善 3-NP 诱导的神经行为缺陷。给予 3-NP 增加纹状体丙二醛（MDA）的水平。用 EGb 761 预处理可防止这种作用。3-NP 处理后，凋亡调节基因表达水平的变化表现为纹状体 Bax 和 Bcl-xl 基因的表达水平分别上调和下调。此外，还观察到纹状体甘油醛-3-磷酸脱氢酶（GAPDH）的表达水平上调。与 3-NP 处理组相比，EGb 761 的预处理导致纹状体 GAPDH 和 Bax 的表达下调以及纹状体 Bcl-xl 表达水平上调。纹状体组织的组织化学检查显示，EGb 761 可显著防止 3-NP 诱导的 SDH 活性抑制。组织病理学检查进一步证实了 EGb 761 对 3-NP 毒性的神经保护作用。总之，这些结果表明，EGb 761 在当前的 HD 模型中具有神经保护作用，这可能与改善能量代谢、抗氧化特性和抗凋亡作用有关。
