Effects of gangliosides on ethanol-induced neurodegeneration in the developing mouse brain
Effects of gangliosides on ethanol-induced neurodegeneration in the developing mouse brain
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DOI：
10.1111/j.1530-0277.2007.00351.x
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Saito, Mitsuo
中科院分区：
文献类型：
--
作者：
Saito, Mariko;Mao, Rui-Fen;Saito, Mitsuo
背景：乙醇暴露诱导发育中啮齿动物脑突触发生过程中的凋亡性神经变性。这一过程已被作为胎儿酒精综合征的模型进行研究。以前，我们已经表明，神经节苷脂和LIGA 20（半合成衍生物的GM 1神经节苷脂）减弱乙醇诱导的细胞凋亡培养的神经元。在本研究中，使用体内新生小鼠模型检查GM 1和LIGA 20对乙醇诱导的凋亡性神经变性的影响。将7日龄C57 BL/6 By（B6 By）小鼠通过腹膜内施用GM 1预处理两次5 mg/kg）、LIGA 20（2.5mg/kg）或盐水，随后皮下注射盐水或乙醇（2.5g/kg）两次，间隔2小时。然后大脑是：（1）在第一次乙醇注射后24小时进行灌注固定，并通过对脑切片进行铜银染色来评估神经变性的程度，或（2）在第一次乙醇注射后8小时进行灌注固定，并用抗切割的用（活化的）半胱天冬酶-3抗体来评估半胱天冬酶-3活化。铜银染色的冠状切片的比较表明，乙醇诱导的广泛的神经变性在B6 By小鼠的前脑整体减少GM 1和LIGA 20预处理。通过银浸渍和活化的半胱天冬酶-3免疫染色检测的神经变性的程度在扣带和压后皮质中定量，这是受乙醇影响最严重的区域。结果表明，GM 1和LIGA 20预处理诱导统计学上显著的减少-约50%的乙醇处理的样品-在银浸渍和活化的半胱天冬酶-3免疫染色。盐水对照组和样品与GM 1或LIGA 20单独治疗之间没有显着差异，观察到：这些结果表明，GM 1和LIGA 20，已被证明是对各种代理商造成的侮辱神经保护，部分衰减乙醇诱导的凋亡神经退行性病变在发育中的小鼠大脑。
Background: Ethanol exposure induces apoptotic neurodegeneration in the developing rodent brain during synaptogenesis. This process has been studied as a model for fetal alcohol syndrome. Previously, we have shown that gangliosides and LIGA20 (a semisynthetic derivative of GM1 ganglioside) attenuate ethanol-induced apoptosis in cultured neurons. In the present study, the effects of GM1 and LIGA20 on ethanol-induced apoptotic neurodegeneration were examined using an in vivo neonatal mouse model.Methods: Seven-day-old C57BL/6By (B6By) mice were pretreated twice with intraperitoneal administration of GM1 (30 mg/kg), LIGA20 (2.5 mg/kg), or saline, followed by subcutaneous injection of either saline or ethanol (2.5 g/kg) twice with a 2 hours interval. Then the brains were: (1) perfusion-fixed 24 hours after the first ethanol injection, and the extent of neurodegeneration was assessed by cupric silver staining of the brain sections, or (2) perfusion-fixed 8 hours after the first ethanol injection, and the sections were immunostained with anti-cleaved (activated) caspase-3 antibody to evaluate caspase-3 activation.Results: The comparison of cupric silver stained coronal sections indicates that ethanol-induced widespread neurodegeneration in the forebrains of B6By mice was reduced overall by GM1 and LIGA20 pretreatments. The extent of neurodegeneration detected by silver impregnation and activated caspase-3 immunostaining was quantified in the cingulate and retrosplenial cortices, which were the regions most severely affected by ethanol. The results indicate that GM1 and LIGA20 pretreatments induced statistically significant reductions-approximately 50% of the ethanol-treated samples-in silver impregnation and activated caspase-3 immunostaining. No significant differences were observed between saline controls and samples treated with GM1 or LIGA20 alone.Conclusions: These results indicate that GM1 and LIGA20, which have been shown to be neuroprotective against insults caused by various agents, partially attenuate ethanol-induced apoptotic neurodegeneration in the developing mouse brain.