Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage

K. Beppu, T. Sasaki, K. Tanaka, A. Yamanaka, Y. Fukazawa, R. Shigemoto, K. Matsui, Neuron 81 (2014) 314–320.

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Journal Article | Published | English
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Abstract
The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the other hand, glial alkalization via optogenetic activation of a proton pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the relief of ischemic brain damage in vivo. Our results suggest that controlling glial pH may be an effective therapeutic strategy for intervention of ischemic brain damage.
Publishing Year
Date Published
2014-01-22
Journal Title
Neuron
Volume
81
Issue
2
Page
314 - 320
ISSN
IST-REx-ID

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Beppu K, Sasaki T, Tanaka K, et al. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron. 2014;81(2):314-320. doi:10.1016/j.neuron.2013.11.011
Beppu, K., Sasaki, T., Tanaka, K., Yamanaka, A., Fukazawa, Y., Shigemoto, R., & Matsui, K. (2014). Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron, 81(2), 314–320. https://doi.org/10.1016/j.neuron.2013.11.011
Beppu, Kaoru, Takuya Sasaki, Kenji Tanaka, Akihiro Yamanaka, Yugo Fukazawa, Ryuichi Shigemoto, and Ko Matsui. “Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release and Ischemic Brain Damage.” Neuron 81, no. 2 (2014): 314–20. https://doi.org/10.1016/j.neuron.2013.11.011.
K. Beppu et al., “Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage,” Neuron, vol. 81, no. 2, pp. 314–320, 2014.
Beppu K, Sasaki T, Tanaka K, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K. 2014. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron. 81(2), 314–320.
Beppu, Kaoru, et al. “Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release and Ischemic Brain Damage.” Neuron, vol. 81, no. 2, Elsevier, 2014, pp. 314–20, doi:10.1016/j.neuron.2013.11.011.

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