Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction
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- 作者：Anna Kiryk (1)
Tomomi Aida (2)
Kohichi Tanaka (2)
Pradeep Banerjee (3)
Grzegorz M. Wilczynski (1)
Ksenia Meyza (1)
Ewelina Knapska (1)
Robert K. Filipkowski (1)
Leszek Kaczmarek (1)
Wojciech Danysz (4) - 关键词：GLT1 KO mice ; GLT1 (+/ ; ) mice ; Glutamate uptake ; Histology ; Immunochemistry ; Behavior
- 刊名：Neurotoxicity Research
- 出版年：2008
- 出版时间：March 2008
- 年：2008
- 卷：13
- 期：1
- 页码：19-30
- 全文大小：675KB
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Tomomi Aida (2)
Kohichi Tanaka (2)
Pradeep Banerjee (3)
Grzegorz M. Wilczynski (1)
Ksenia Meyza (1)
Ewelina Knapska (1)
Robert K. Filipkowski (1)
Leszek Kaczmarek (1)
Wojciech Danysz (4)
1. Nencki Institute of Experimental Biology, Pasteura 3, PL-02093, Warsaw, Poland
2. Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, 113-851, Bunkyo-Ku, Tokyo, Japan
3. Forest Research Institute, 07311, Jersey City, NJ, USA
4. In Vivo Pharmacology, Merz Pharmaceuticals, Eckenheimer Landstrasse 100, D-61130, Frankfurt am Main, Germany - ISSN：1476-3524
文摘
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.