Cognitive impairment in mice over-expressing γ-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. GATI over-expressing mice (NA) were generated, in which GATI 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 GATI 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 GATI in the neural control of cognitive processes, and indicate great potential for GATI as a clinical target of cognitive disorders.