Frischknecht Ulrich, Hermann Derik, Tunc-Skarka Nuran, Wang Guo-Ying, Sack Markus, van Eijk Julia, Demirakca Traute, Falfan-Melgoza Claudia, Krumm Bertram, Dieter Sandra, Spanagel Rainer, Kiefer Falk, Mann Karl F, Sommer Wolfgang H, Ende Gabriele, Weber-Fahr Wolfgang
Department of Addictive Behavior and Addiction Medicine , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Neuroimaging , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Alcohol Clin Exp Res. 2017 Feb;41(2):323-333. doi: 10.1111/acer.13308. Epub 2017 Jan 18.
Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats.
Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence.
In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model.
Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.
长期饮酒和戒酒都会导致神经组织损伤，而在戒酒期间部分损伤会恢复。本研究调查了在海马体急性戒酒过程中，谷氨酸能化合物、神经元完整性标志物以及灰质体积与戒酒相关的变化，海马体是人类和大鼠酒精依赖形成和维持的关键区域。
酒精依赖患者（N = 39）在最后一次饮酒后24小时内以及戒酒2周后接受磁共振成像（MRI）和磁共振波谱（MRS）测量。健康对照者（N = 34）的MRI和MRS数据仅采集一次。我们严格的质量标准使得患者第一次测量获得了N = 15份可用波谱，第二次测量获得了N = 21份，健康对照者获得了N = 19份。采用转化研究方法，慢性间歇性乙醇暴露大鼠及其相应对照（每组8只）进行了5次MRS测量，涵盖基线、中毒、戒断12小时和60小时以及戒酒3周。
在两个物种中，戒酒早期海马体中谷氨酸能代谢标志物水平较高与灰质体积较低相关。在有严重酒精戒断症状的患者中，中毒期间N - 乙酰天门冬氨酸水平降低的趋势在戒酒2周后仍然存在。在我们的动物模型中，戒酒期间观察到谷氨酸与谷氨酰胺的比例更高。
由于统计效力有限，我们将结果视为初步结果，并在戒断诱导的高谷氨酸能神经毒性假说、酒精诱导的神经变化以及戒酒对海马体组织完整性的训练相关效应的框架内进行讨论。
