The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice
Abstract
The glial glutamate transporter EAAT2 is primarily responsible for clearance of glutamate from the synaptic cleft and loss of EAAT2 has been previously reported in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. The loss of functional EAAT2 could lead to the accumulation of extracellular glutamate, resulting in cell death known as excitotoxicity. However, it is still unknown whether it is a primary cause in the cascade leading to neuron degeneration or a secondary event to cell death. The goals of this study were to generate transgenic mice overexpressing EAAT2 and then to cross these mice with the ALS-associated mutant SOD1(G93A) mice to investigate whether supplementation of the loss of EAAT2 would delay or rescue the disease progression. We show that the amount of EAAT2 protein and the associated Na+-dependent glutamate uptake was increased about 2-fold in our EAAT2 transgenic mice. The transgenic EAAT2 protein was properly localized to the cell surface on the plasma membrane. Increased EAAT2 expression protects neurons from L-glutamate induced cytotoxicity and cell death in vitro. Furthermore, our EAAT2/G93A double transgenic mice showed a statistically significant (14 days) delay in grip strength decline but not in the onset of paralysis, body weight decline or life span when compared with G93A littermates. Moreover, a delay in the loss of motor neurons and their axonal morphologies as well as other events including caspase-3 activation and SOD1 aggregation were also observed. These results suggest that the loss of EAAT2 may contribute to, but does not cause, motor neuron degeneration in ALS.
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Cites
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Rothstein, J. D., Dykes-Hoberg, M., Pardo, C. A., Bristol, L. A., Jin, L., Kuncl, R. W., Kanai, Y., Hediger, M. A., Wang, Y., Schielke, J. P., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80086-0 · Cited by 2,534
Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1
Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahashi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., et al. (1997) · Science · doi:10.1126/science.276.5319.1699 · Cited by 1,752
Localization of neuronal and glial glutamate transporters
Rothstein, J. D., Martin, L., Levey, A. I., Dykes-Hoberg, M., Jin, L., Wu, D., Nash, N., & Kuncl, R. W. (1994) · Neuron · doi:10.1016/0896-6273(94)90038-8 · Cited by 1,702
Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis
Rothstein, J. D., Van Kammen, M., Levey, A. I., Martin, L. J., & Kuncl, R. W. (1995) · Annals of Neurology · doi:10.1002/ana.410380114 · Cited by 1,471
Wong, P. C., Pardo, C. A., Borchelt, D. R., Lee, M. K., Copeland, N. G., Jenkins, N. A., Sisodia, S. S., Cleveland, D. W., & Price, D. L. (1995) · Neuron · doi:10.1016/0896-6273(95)90259-7 · Cited by 1,445
Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80272-x · Cited by 1,341
Koh, J. Y., & Choi, D. W. (1987) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(87)90041-0 · Cited by 1,260
Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1
Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S. D., Ohama, E., Reaume, A. G., Scott, R. W., & Cleveland, D. W. (1998) · Science · doi:10.1126/science.281.5384.1851 · Cited by 1,228
Decreased Glutamate Transport by the Brain and Spinal Cord in Amyotrophic Lateral Sclerosis
Rothstein, J. D., Martin, L. J., & Kuncl, R. W. (1992) · New England Journal of Medicine · doi:10.1056/nejm199205283262204 · Cited by 1,177
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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
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127
SLC Transporters as Therapeutic Targets: Emerging Opportunities
Lin, L., Yee, S. W., Kim, R. B., & Giacomini, K. M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4626 · Cited by 835
Current hypotheses for the underlying biology of amyotrophic lateral sclerosis
Rothstein, J. D. (2009) · Annals of Neurology · doi:10.1002/ana.21543 · Cited by 703
Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
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Metadata
- Authors
- Guo, H.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-08-05
- Volume
- 12
- Issue
- 19
- Pages
- 2519-2532
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2151927746
- Cited by
- 284
- References
- 47
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- closed
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- Guo, H. (2003). Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddg267
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