Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1108, USA.
Biol Psychiatry. 2010 May 1;67(9):823-30. doi: 10.1016/j.biopsych.2009.12.018. Epub 2010 Feb 4.
Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown. Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol.
Following 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-beta (TGF-beta) staining were carried out, and reversal learning in the Morris water maze was assessed.
Fluoro-Jade B staining indicating neurodegeneration was most extensive in the ventral hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective in the EC but not in the dentate gyrus of the hippocampus. In parallel, binge alcohol exposure suppressed TGF-beta expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-beta in the EC only. Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning.
Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-beta in alcohol-induced neurodegeneration.
谷氨酰胺能神经传递与酒精引起的神经退行性变和认知障碍的机制有关，但潜在的机制仍不清楚。在这里，我们研究了 II 型代谢型谷氨酸受体激动剂 LY379268 是否可以预防 binge-like 酒精暴露的大鼠模型中的神经元死亡和学习缺陷。
在接受 LY379268 或载体处理的同时进行 4 天 binge 酒精暴露后，进行 Fluoro-Jade B 和转化生长因子-β（TGF-β）染色，并评估 Morris 水迷宫中的反转学习。
Fluoro-Jade B 染色表明神经退行性变在腹侧海马体和内嗅皮层（EC）中最为广泛。LY379268 在 EC 中具有强大的神经保护作用，但在海马体的齿状回中则没有。平行地， binge 酒精暴露抑制了 EC 和齿状回中的 TGF-β表达，而 LY379268 仅增加了 EC 中的 TGF-β。最后，LY379268 的神经保护作用伴随着空间反转学习缺陷的预防。
我们的数据支持 II 型代谢型谷氨酸受体激动剂和 TGF-β在酒精引起的神经退行性变中的神经保护作用。
