Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 521, 6701, Szeged, Hungary.
Cell Stress Chaperones. 2010 Nov;15(6):807-17. doi: 10.1007/s12192-010-0188-8. Epub 2010 May 12.
Alcohol induces degeneration of neurons and inhibits neurogenesis in the brain. Small heat shock proteins are able to protect neurons in cerebral ischemia and oxidative stress. In this study, we investigated the neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic ethanol administrations using transgenic mice overexpressing the human Hsp27 protein. Transgenic mice and wild-type littermates were injected with 2 g/kg ethanol intraperitoneally, and then motor coordination and muscle strength were analyzed using different behavioral tests, such as footprint analysis, balance beam, and inverted screen tests. Ethanol-injected transgenic mice showed similar footprints to control saline-injected mice, did not fall of the beam, and were able to climb to the top of the inverted screen, while wild-type mice showed ataxia and incoordination after ethanol injection. The effect of Hsp27 on chronic ethanol consumption was also investigated. Drinking water of mice was replaced by a 20% ethanol solution for 5 weeks, and then brain sections were stained with Fluoro Jade C staining. We found significantly lesser amount of degenerating neurons in the brain of ethanol-drinking transgenic mice compared to wild-type mice. We conclude that Hsp27 can protect neurons against the acute and chronic toxic effects of ethanol.
酒精会导致大脑神经元变性和神经发生抑制。小热休克蛋白能够保护脑缺血和氧化应激中的神经元。在这项研究中,我们使用过表达人 Hsp27 蛋白的转基因小鼠,研究了小热休克蛋白 Hsp27 在急性和慢性乙醇给药后的神经保护作用。转基因小鼠和野生型同窝仔鼠经腹腔内注射 2g/kg 乙醇,然后使用足迹分析、平衡木和倒屏试验等不同行为试验分析运动协调和肌肉力量。乙醇注射的转基因小鼠的足迹与对照生理盐水注射的小鼠相似,不会从梁上掉落,并且能够爬到倒屏的顶部,而野生型小鼠在乙醇注射后表现出共济失调和不协调。我们还研究了 Hsp27 对慢性乙醇消耗的影响。用 20%乙醇溶液替代小鼠的饮用水 5 周,然后用 Fluoro Jade C 染色对脑切片进行染色。与野生型小鼠相比,饮酒的转基因小鼠大脑中变性神经元的数量明显减少。我们得出结论,Hsp27 可以保护神经元免受乙醇的急性和慢性毒性作用。