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Changes of metabolite profile in kainic acid induced hippocampal injury in rats measured by HRMAS NMR

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Abstract

The solid-state high resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) technique was applied in this work to characterize and quantify the neurochemical changes in the rat hippocampus (CA1 or CA3) after local administration of kainic acid (KA). Intact tissue samples obtained from the KA treated and control brain samples were analyzed using HRMAS NMR. Metabolite profiles from NMR spectra of KA treated and control samples revealed the statistical significant decrease of N-acetylaspartate (NAA) and an increase of choline derivatives in the CA1 and CA3 directly receiving KA injection. Less extensive KA-induced metabolic changes were found in the hippocampi sample from the area contralateral to the site receiving KA administration. These results provided quantitative metabolic information on KA-induced neuronal loss and cell breakdown. In addition, the present study also revealed increased level of γ-aminobutyric acid (GABA) and glutamate after KA treatment, suggesting that the cellular release of inhibitory and excitatory amino acids can be quantified using this method. KA induced microglia activation was evidenced by increased level of myo-insitol (myo-I). This study demonstrates that ex vivo HRMAS NMR is a useful tool for analyzing and quantifying changes of neurochemistry and cerebral metabolism in the intact brain.

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Abbreviations

KA:

Kainic acid

HRMAS:

High resolution magic angle spinning

NMR:

Nuclear magnetic resonance

MRS:

Magnetic resonance spectroscopy

NAA:

N-acetyl-aspartate

Cho:

Choline

PC:

Phosphocholine

GPC:

Glyocerphosphocholine

Cre:

Creatine

myo-I:

Myo-inositol

Glu:

Glutamate

Gln:

Glutamine

GABA:

γ-aminobutyric acid

DANTE:

Delays alternating with nutations for tailored excitation

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Authors and Affiliations

  1. Department of Radiology and Frederick Philips MR Research Center, Emory University School of Medicine, 1364 Clifton Road, Atlanta, Georgia, 30322, USA

    Hui Mao & Xiaoxia Wang

  2. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, 30322, USA

    Donna Toufexis & Agnès Lacreuse

  3. Department of Psychology, University of Massachusetts-Amherst, Amherst, 01003, USA

    Agnès Lacreuse

  4. Department of Chemistry and Center of NMR Research, Emory University, Atlanta, Georgia, 30322, USA

    Shaoxiong Wu

Authors
  1. Hui Mao
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  2. Donna Toufexis
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  3. Xiaoxia Wang
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  4. Agnès Lacreuse
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  5. Shaoxiong Wu
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Correspondence to Hui Mao.

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Mao, H., Toufexis, D., Wang, X. et al. Changes of metabolite profile in kainic acid induced hippocampal injury in rats measured by HRMAS NMR. Exp Brain Res 183, 477–485 (2007). https://doi.org/10.1007/s00221-007-1061-6

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  • DOI: https://doi.org/10.1007/s00221-007-1061-6

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