Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats

被引：29

作者：

Frischknecht, Ulrich ^{[1
]}

Hermann, Derik ^{[1
]}

Tunc-Skarka, Nuran ^{[2
]}

Wang, Guo-Ying ^{[2
]}

Sack, Markus ^{[2
]}

van Eijk, Julia ^{[2
]}

Demirakca, Traute ^{[2
]}

Falfan-Melgoza, Claudia ^{[3
]}

Krumm, Bertram ^{[4
]}

Dieter, Sandra ^{[5
]}

Spanagel, Rainer ^{[5
]}

Kiefer, Falk ^{[1
]}

Mann, Karl F. ^{[1
]}

Sommer, Wolfgang H. ^{[1
,5
]}

Ende, Gabriele ^{[2
]}

Weber-Fahr, Wolfgang ^{[3
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, Sq J5, D-68159 Mannheim, Germany

[2] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Neuroimaging, Mannheim, Germany

[3] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Res Grp Translat Imaging, Mannheim, Germany

[4] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Biostat, Mannheim, Germany

[5] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany

来源：

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH | 2017年 / 41卷 / 02期

关键词：

Alcohol Withdrawal; Magnetic Resonance Spectroscopy; Hippocampus; Glutamate; Gray Matter; MAGNETIC-RESONANCE-SPECTROSCOPY; GAMMA-AMINOBUTYRIC-ACID; BRAIN VOLUME; N-ACETYLASPARTATE; WATER-CONTENT; ABSTINENCE; DEPENDENCE; PLASTICITY; RECOVERY; NEUROTRANSMISSION;

D O I：

10.1111/acer.13308

中图分类号：

R194 [卫生标准、卫生检查、医药管理];

学科分类号：

摘要：

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

引用

页码：323 / 333

页数：11

共 59 条

[11] Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure [J].