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使用体内氢磁共振波谱法研究乙醇暴露对谷氨酸释放增强的转基因小鼠模型神经化学特征的影响。

Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo H MRS.

作者信息

Wang Wen-Tung, Lee Phil, Hui Dongwei, Michaelis Elias K, Choi In-Young

机构信息

Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA.

Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.

出版信息

Neurochem Res. 2019 Jan;44(1):133-146. doi: 10.1007/s11064-018-2658-9. Epub 2018 Oct 17.

Abstract

Ethanol (EtOH) intake leads to modulation of glutamatergic transmission, which may contribute to ethanol intoxication, tolerance and dependence. To study metabolic responses to the hyper glutamatergic status at synapses during ethanol exposure, we used Glud1 transgenic (tg) mice that over-express the enzyme glutamate dehydrogenase in brain neurons and release excess glutamate (Glu) in synapses. We measured neurochemical changes in the hippocampus and striatum of tg and wild-type (wt) mice using proton magnetic resonance spectroscopy before and after the animals were fed with diets within which EtOH constituting up to 6.4% of total calories for 24 weeks. In the hippocampus, the EtOH diet led to significant increases in concentrations of EtOH, glutamine (Gln), Glu, phosphocholine (PCho), taurine, and Gln + Glu, when compared with their baseline concentrations. In the striatum, the EtOH diet led to significant increases in concentrations of GABA, Gln, Gln + Glu, and PCho. In general, neurochemical changes were more pronounced in the striatum than the hippocampus in both tg and wt mice. Overall neurochemical changes due to EtOH exposure were very similar in tg and wt mice. This study describes time courses of neurochemical profiles before and during chronic EtOH exposure, which can serve as a reference for future studies investigating ethanol-induced neurochemical changes.

摘要

摄入乙醇(EtOH)会导致谷氨酸能传递的调节,这可能与乙醇中毒、耐受性和依赖性有关。为了研究乙醇暴露期间突触处高谷氨酸能状态的代谢反应,我们使用了Glud1转基因(tg)小鼠,这些小鼠在脑神经元中过度表达谷氨酸脱氢酶,并在突触中释放过量的谷氨酸(Glu)。在给动物喂食含乙醇量高达总热量6.4%的饮食24周之前和之后,我们使用质子磁共振波谱测量了tg和野生型(wt)小鼠海马体和纹状体中的神经化学变化。在海马体中,与基线浓度相比,乙醇饮食导致乙醇、谷氨酰胺(Gln)、谷氨酸、磷酸胆碱(PCho)、牛磺酸以及Gln + Glu的浓度显著增加。在纹状体中,乙醇饮食导致γ-氨基丁酸(GABA)、Gln、Gln + Glu和PCho的浓度显著增加。总体而言,在tg和wt小鼠中,纹状体中的神经化学变化比海马体中更明显。tg和wt小鼠中由于乙醇暴露引起的总体神经化学变化非常相似。本研究描述了慢性乙醇暴露之前和期间神经化学特征的时间进程,可为未来研究乙醇诱导的神经化学变化提供参考。

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