Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1).
There is increasing evidence that GABAergic system plays an important role in the neural control of learning and memory processes. GAT1 over-expressing mice (NA) were generated, in which GAT1 is under the control of a neuron-specific enolase (NSE) promoter, to investigate effects of GABA transporter on cognitive function. Our results revealed that NA mice displayed cognitive deterioration in associative learning ability and new object recognition retention, compared with the wild-type littermates (WT2). However, the impaired cognitive function of transgenic mice could be rescued after chronic administration of GAT1 selective inhibitor for 6 days. In addition, there was no change of the expression of NMDA receptors in NA mice. Taken together, we show a potentially important role for GAT1 in the neural control of cognitive processes, and indicate great potential for GAT1 as a clinical target of cognitive disorders.
Hu
Jia-Hua
JH
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
Ma
Ying-Hua
YH
Jiang
Jie
J
Yang
Na
N
Duan
Shu-hui
SH
Jiang
Zhi-Hua
ZH
Mei
Zhen-Tong
ZT
Fei
Jian
J
Guo
Li-He
LH
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D027361:Organic Anion Transporters; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D016194:Receptors, N-Methyl-D-Aspartate; C493414:Slc6a1 protein, mouse; D010751:Phosphopyruvate Hydratase