The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
A Neuronal Glutamate Transporter Contributes to Neurotransmitter GABA Synthesis and Epilepsy
Open accessAbstract
The predominant neuronal glutamate transporter, EAAC1 (for excitatory amino acid carrier-1), is localized to the dendrites and somata of many neurons. Rare presynaptic localization is restricted to GABA terminals. Because glutamate is a precursor for GABA synthesis, we hypothesized that EAAC1 may play a role in regulating GABA synthesis and, thus, could cause epilepsy in rats when inactivated. Reduced expression of EAAC1 by antisense treatment led to behavioral abnormalities, including staring-freezing episodes and electrographic (EEG) seizures. Extracellular hippocampal and thalamocortical slice recordings showed excessive excitability in antisense-treated rats. Patch-clamp recordings of miniature IPSCs (mIPSCs) conducted in CA1 pyramidal neurons in slices from EAAC1 antisense-treated animals demonstrated a significant decrease in mIPSC amplitude, indicating decreased tonic inhibition. There was a 50% loss of hippocampal GABA levels associated with knockdown of EAAC1, and newly synthesized GABA from extracellular glutamate was significantly impaired by reduction of EAAC1 expression. EAAC1 may participate in normal GABA neurosynthesis and limbic hyperexcitability, whereas epilepsy can result from a disruption of the interaction between EAAC1 and GABA metabolism.
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Cites
Glutamate neurotoxicity and diseases of the nervous system
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Self-citationEpilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1
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Self-citationPrimary structure and functional characterization of a high-affinity glutamate transporter
Kanai, Y., & Hediger, M. A. (1992) · Nature · doi:10.1038/360467a0 · Cited by 1,332
Cloning and expression of a rat brain L-glutamate transporter
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Self-citationAn excitatory amino-acid transporter with properties of a ligand-gated chloride channel
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Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex
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Cited by
β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
Rothstein, J. D., Patel, S., Regan, M. R., Haenggeli, C., Huang, Y. H., Bergles, D. E., Jin, L., Dykes Hoberg, M., Vidensky, S., Chung, D. S., et al. (2005) · Nature · doi:10.1038/nature03180 · Cited by 1,518
Self-citationSelective induction of astrocytic gliosis generates deficits in neuronal inhibition
Ortinski, P. I., Dong, J., Mungenast, A., Yue, C., Takano, H., Watson, D. J., Haydon, P. G., & Coulter, D. A. (2010) · Nature Neuroscience · doi:10.1038/nn.2535 · Cited by 495
Self-citationNeuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse
Aoyama, K., Suh, S. W., Hamby, A. M., Liu, J., Chan, W. Y., Chen, Y., & Swanson, R. A. (2006) · Nature Neuroscience · doi:10.1038/nn1609 · Cited by 484
Pajarillo, E., Rizor, A., Lee, J., Aschner, M., & Lee, E. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.03.002 · Cited by 478
Neuroinflammation and regulation of glial glutamate uptake in neurological disorders
Tilleux, S., & Hermans, E. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21325 · Cited by 381
Metadata
- Authors
- Sepkuty, J. P., Cohen, A. S., Eccles, C., Rafiq, A., Behar, K., Ganel, R., Coulter, D. A., & Rothstein, J. D.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 6372-6379
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2103064125
- Cited by
- 264
- References
- 49
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: A Neuronal Glutamate Transporter Contributes to Neurotransmitter GABA Synthesis and Epilepsy. https://app.cochat.ai/papers/10.1523/jneurosci.22-15-06372.2002
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- Sepkuty, J. P., Cohen, A. S., Eccles, C., Rafiq, A., Behar, K., Ganel, R., Coulter, D. A., & Rothstein, J. D. (2002). A Neuronal Glutamate Transporter Contributes to Neurotransmitter GABA Synthesis and Epilepsy. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.22-15-06372.2002
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