Cognitive impairment in mice over-expressing γ-aminobutyric acid transporter I (GAT1)
Abstract
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.
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Reducing hippocampal GABA levels impairs learning and memory.
“Furthermore, reducing hippocampal GABA levels impairs learning and memory [120, 121], and silencing inhibitory interneurons in the dentate gyrus prevents both encoding of new memories and recall of old memories [122].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [120]
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- Authors
- Hu, J.-H., Ma, Y.-H., Jiang, J., Yang, N., Duan, S.-H., Jiang, Z.-H., Mei, Z.-T., Fei, J., & Guo, L.-H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Fei, Jian
- Guo, Li-He
- Venue
- NeuroReport
- Published
- 2004-01
- Volume
- 15
- Issue
- 1
- Pages
- 9-12
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W2087605748
- Cited by
- 26
- References
- 17
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2012: 5
- FWCI
- 0.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- GABA transporter 1, cognitive impairment, associative learning, object recognition memory, GABAergic system, neuron-specific enolase promoter, NMDA receptor, transgenic mice, learning and memory
- MeSH terms
- Animals, Avoidance Learning, Carrier Proteins, Cerebral Cortex, Cognition Disorders, Gene Expression Regulation, Hippocampus, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Phosphopyruvate Hydratase, Receptors, N-Methyl-D-Aspartate, Membrane Transport Proteins, Organic Anion Transporters, GABA Plasma Membrane Transport Proteins, Mice
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