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In vivo Proton NMR Spectroscopy of Genetic Mouse Models BALB/cJ and C57BL/6By: Variation in Hippocampal Glutamate Level and the Metabotropic Glutamate Receptor, Subtype 7 (Grm7) Gene

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Abstract

Glutamatergic neurotransmission in the brain is modulated by metabotropic glutamate receptors (mGluR). In recent studies, we identified a cis-regulated variant of a gene (Grm7) which codes for mGluR subtype 7 (mGluR7), a presynaptic inhibitory receptor. The genetic variant derived from the BALB/cJ mouse strain (Grm7 BALB/cJ) codes for higher abundance of mGluR7 mRNA in the hippocampus than the C57BL/6By strain-derived variant (Grm7 C57BL/6By). Here, we used localized in vivo 1H NMR spectroscopy to test the hypothesis that Grm7 BALB/cJ is also associated with lower glutamate concentration in the same brain region. All data were obtained on a 7.0 T Agilent (Santa Clara, CA, USA) 40-cm bore system using experimentally naive adult male inbred C57BL/6By, BALB/cJ, and congenic mice (B6By.C.6.132.54) constructed in our laboratory carrying Grm7 BALB/cJ on C57BL/6By genetic background. The voxel of interest size was 6 μL (1 × 2 × 3 mm3) placed in the hippocampal CA1 region. The results showed that the hippocampal level of glutamate in the congenic mouse strain was significantly lower than that in the background C57BL/6By strain which carried the Grm7 C57BL/6By allele. Because the two inbred strains are genetically highly similar except at the region of the Grm7 gene, the results raise the possibility that allelic variation at the Grm7 locus contributes to the strain differences in both hippocampal mRNA abundance and glutamate level which may modulate complex behavioral traits, such as learning and memory, addiction, epilepsy, and mood disorders.

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Fig. 1
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Abbreviations

Ala:

alanine

ANOVA:

analysis of variance

Asp:

aspartate

B6By:

C57BL/6By

B6By.C:

B6By.C.6.132.54

C:

BALB/cJ

Cr:

creatine

CRLB:

Cramér-Rao lower bounds

GABA:

γ-aminobutyric acid

Glc:

glucose

Gln:

glutamine

Glu:

glutamate

GPC:

glycerophosphorylcholine

Grm7 :

glutamate receptor metabotropic subtype 7

GSH:

glutathione

mI:

myo-inositol

NAA:

N-acetylaspartate

NAAG:

N-acetylaspartylglutamate

PCh:

phosphorylcholine

PCr:

phosphocreatine

PE:

phosphorylethanolamine

RF:

radiofrequency

Tau:

taurine

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Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Center for Advanced Brain Imaging, Nathan Kline Institute, Orangeburg, NY, USA

    David N. Guilfoyle & Scott Gerum

  2. Laboratory of Neurobehavioral Genetics, Nathan Kline Institute, Orangeburg, NY, USA

    Csaba Vadasz

  3. Department of Psychiatry, New York University School of Medicine, New York, NY, USA

    Csaba Vadasz

  4. Department of Radiology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA

    David N. Guilfoyle

  5. 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Csaba Vadasz

Authors
  1. David N. Guilfoyle
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  2. Scott Gerum
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  3. Csaba Vadasz
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Corresponding author

Correspondence to Csaba Vadasz.

Additional information

David N Guilfoyle and Csaba Vadasz contributed equally to this work.

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Guilfoyle, D.N., Gerum, S. & Vadasz, C. In vivo Proton NMR Spectroscopy of Genetic Mouse Models BALB/cJ and C57BL/6By: Variation in Hippocampal Glutamate Level and the Metabotropic Glutamate Receptor, Subtype 7 (Grm7) Gene. J Mol Neurosci 53, 135–141 (2014). https://doi.org/10.1007/s12031-013-0211-5

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  • DOI: https://doi.org/10.1007/s12031-013-0211-5

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