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Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS

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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.

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Funding

This study was funded by National Institute on Aging (AG 12993, AG 035982), Kansas City Area Life Sciences Institute (KCALSI-07-13).

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Authors and Affiliations

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

    Wen-Tung Wang, Phil Lee & In-Young Choi

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

    Phil Lee & In-Young Choi

  3. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

    In-Young Choi

  4. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA

    Dongwei Hui & Elias K. Michaelis

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  1. Wen-Tung Wang
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  2. Phil Lee
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  3. Dongwei Hui
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  4. Elias K. Michaelis
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Correspondence to In-Young Choi.

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Special issue: In honor of Elias K. Michaelis.

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Wang, WT., Lee, P., Hui, D. et al. Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS. Neurochem Res 44, 133–146 (2019). https://doi.org/10.1007/s11064-018-2658-9

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  • DOI: https://doi.org/10.1007/s11064-018-2658-9

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