Department of Biochemistry and Biotechnology Core Facility, Kansas State University Manhattan, KS, USA.
Front Mol Neurosci. 2013 May 28;6:14. doi: 10.3389/fnmol.2013.00014. eCollection 2013.
The brain is one of the major targets of alcohol actions. Most of the excitatory synaptic transmission in the central nervous system is mediated by N-methyl-D-aspartate (NMDA) receptors. However, one of the most devastating effects of alcohol leads to brain shrinkage, loss of nerve cells at specific regions through a mechanism involving excitotoxicity, oxidative stress. Earlier studies have indicated that chronic exposure to ethanol both in vivo and in vitro, increases NR1 and NR2B gene expression and their polypeptide levels. The effect of alcohol and molecular changes on the regulatory process, which modulates NMDAR functions including factors altering transcription, translation, post-translational modifications, and protein expression, as well as those influencing their interactions with different regulatory proteins (downstream effectors) are incessantly increasing at the cellular level. Further, I discuss the various genetically altered mice approaches that have been used to study NMDA receptor subunits and their functional implication. In a recent countable review, epigenetic dimension (i.e., histone modification-induced chromatin remodeling and DNA methylation, in the process of alcohol related neuroadaptation) is one of the key molecular mechanisms in alcohol mediated NMDAR alteration. Here, I provide a recount on what has already been achieved, current trends and how the future research/studies of the NMDA receptor might lead to even greater engagement with many possible new insights into the neurobiology and treatment of alcoholism.
大脑是酒精作用的主要靶器官之一。中枢神经系统中的大多数兴奋性突触传递都是由 N-甲基-D-天冬氨酸（NMDA）受体介导的。然而，酒精最具破坏性的影响之一是导致脑萎缩，通过涉及兴奋性毒性和氧化应激的机制，特定区域的神经细胞丧失。早期研究表明，体内和体外慢性暴露于乙醇都会增加 NR1 和 NR2B 基因表达及其多肽水平。酒精和分子变化对调节过程的影响，包括改变转录、翻译、翻译后修饰和蛋白质表达的因素，以及影响其与不同调节蛋白（下游效应物）相互作用的因素，在细胞水平上不断增加。此外，我讨论了已经用于研究 NMDA 受体亚基及其功能意义的各种基因改变小鼠方法。在最近的一篇综述中，表观遗传维度（即与酒精相关的神经适应过程中组蛋白修饰诱导的染色质重塑和 DNA 甲基化）是酒精介导的 NMDA 受体改变的关键分子机制之一。在这里，我提供了已经取得的成就、当前趋势的回顾，以及 NMDA 受体的未来研究/研究如何可能导致对神经生物学和酒精中毒治疗的许多新见解的更大关注。
