Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction
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GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the brain. In the present study, glutamate transporter 1-deficient GLT1 homozygous (-/-) and heterozygous (+/-) mice were investigated with the intention that they may provide a model of hyperglutamatergic state resulting in various behavioral alterations. The GLT1 (-/-) mice had lower body and brain weight, mild neuronal loss in CA1 hippocampal region as well as focal gliosis and severe focal neuronal paucity in layer II of the neocortex. The short life-span of GLT1 (-/-) precluded us from systematic behavioral studies in these mice. In contrast, GLT1 (+/-) mice exhibiting a 59% decrease in GLT1 immunoreactivity in their brain tissue, showed no apparent morphological brain abnormalities, and their life-span was not markedly different from controls. Behavior ally, GLT1 (+/-) presented moderate behavioral alterations compared to their wildtype littermates, such as: mild sensorimotor impairment, hyperlocomotion (at 3 month of age only), lower anxiety (at 6 months), better learning of cue-based fear conditioning but worse context-based fear conditioning. Our results suggest that GLT1 (+/-) mice may serve as a potentially useful model to study neurodegenerative disease conditions with mild hyperglutamatergic activity.
KeywordsGLT1 KO mice GLT1 (+/-) mice Glutamate uptake Histology Immunochemistry Behavior
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- Accili D, CS Fishburn, J Drago, H Steiner, JE Lachowicz, BH Park, EB Gauda, EJ Lee, MH Cool, DR Sibley, CR Gerfen, H Westphal and S Fuchs (1996) A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice.Proc. Natl. Acad. Sci. USA 93, 1945–1949.PubMedCrossRefGoogle Scholar
- Danysz W, CG Parsons, I Bresink and G Quack (1995a) Glutamate in CNS disorders — a revived target for drug development.Drug News Perspect. 8, 261–277.Google Scholar
- Tanaka K, K Watase, T Manabe, K Yamada, M Watanabe, K Takahashi, H Iwama, T Nishikawa, N Ichihara, T Kikuchi, S Okuyama, N Kawashima, S Hori, M Takimoto and K Wada (1997a) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.Science 276, 1699–1702.PubMedCrossRefGoogle Scholar