局部生成的乙醛参与了乙醇介导的海马体 LTP 抑制。
Locally-generated acetaldehyde is involved in ethanol-mediated LTP inhibition in the hippocampus.
机构信息
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States.
出版信息
Neurosci Lett. 2013 Mar 14;537:40-3. doi: 10.1016/j.neulet.2013.01.018. Epub 2013 Jan 24.
Abstract
Consistent with the ability of severe alcohol intoxication to impair memory, high concentrations of ethanol (60mM) acutely inhibit long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. To account for this, we hypothesized that local metabolism to acetaldehyde may contribute to the effects of high ethanol on synaptic function. However, sodium azide, a catalase inhibitor, and allyl sulfide, an inhibitor of cytochrome P450 2E1 (CYP2E1), failed to overcome LTP inhibition by 60mM ethanol. In contrast, LTP was successfully induced in the presence of ethanol plus 4-methylpyrazole (4MP), an inhibitor of alcohol dehydrogenase, suggesting that local metabolism via alcohol dehydrogenase contributes to synaptic effects. Furthermore, exogenously administered acetaldehyde overcame the effects of 4MP on LTP inhibition mediated by ethanol. These observations indicate that acetaldehyde generated by local metabolism within the hippocampus participates in the synaptic dysfunction associated with severe alcohol intoxication.
摘要
与重度酒精中毒损害记忆的能力一致，高浓度乙醇（60mM）可急性抑制大鼠海马切片 CA1 区的长时程增强（LTP）。考虑到这一点，我们假设局部代谢为乙醛可能有助于高乙醇对突触功能的影响。然而，氰化钠，一种过氧化氢酶抑制剂，和烯丙基硫醚，一种细胞色素 P450 2E1（CYP2E1）抑制剂，并不能克服 60mM 乙醇对 LTP 的抑制作用。相比之下，在乙醇加 4-甲基吡唑（4MP）存在的情况下成功诱导了 LTP，4MP 是一种抑制醇脱氢酶的物质，表明通过醇脱氢酶的局部代谢有助于突触效应。此外，外源性给予乙醛可克服 4MP 对乙醇介导的 LTP 抑制的影响。这些观察结果表明，海马内局部代谢产生的乙醛参与了与重度酒精中毒相关的突触功能障碍。
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