Impaired Glutamatergic and GABAergic Function at Early Age in AβPPswe-PS1dE9 Mice: Implications for Alzheimer's Disease

Article type: Short Communication

Authors: Tiwari, Vivek | Patel, Anant B.^{; *}

Affiliations: NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India

Correspondence: [*] Correspondence to: Dr. Anant B. Patel, NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, Hyderabad 500 007, India. Tel.: +91 40 27192838; Fax: +91 40 27160310; E-mail: abpatel@ccmb.res.in.

Abstract: Preclinical diagnosis of Alzheimer's disease is a major challenge. The present study evaluates glutamatergic and GABAergic neurotransmitter energetics at the age of 6 months in AβPPswe-PS1dE9 mouse model of Alzheimer's disease by using 1H-[13C]-NMR spectroscopy together with infusion of [1,6-13C2]glucose. NMR analysis suggested no significant derangement in neurochemical profile in AβPPswe-PS1dE9 mice. However, decrease in labeling of glutamate-C4, GABA-C2 and glutamine-C4 at early infusion-time together with no change in labeling at steady state from [1,6-13C2]glucose indicates an impaired glutamatergic and GABAergic glucose oxidation and neurotransmitter cycle in AβPPswe-PS1dE9 mice. These findings may have implication in preclinical diagnosis of Alzheimer's disease.

Keywords: Alzheimer's disease, GABA, glutamate, neuron-glia trafficking, neurotransmitter cycle, nuclear magnetic resonance spectroscopy

DOI: 10.3233/JAD-2011-111502

Journal: Journal of Alzheimer's Disease, vol. 28, no. 4, pp. 765-769, 2012