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

Kaoru Beppu, Takuya Sasaki, Kenji Tanaka, Akihiro Yamanaka, Yugo Fukazawa, Ryuichi Shigemoto, Ko Matsui

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)314-320
Number of pages7
JournalNeuron
Volume81
Issue number2
DOIs
Publication statusPublished - 2014 Jan 22

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Optogenetics
Acidosis
Neuroglia
Glutamic Acid
Brain
Ischemia
Proton Pumps
Cations
Protons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. / Beppu, Kaoru; Sasaki, Takuya; Tanaka, Kenji; Yamanaka, Akihiro; Fukazawa, Yugo; Shigemoto, Ryuichi; Matsui, Ko.

In: Neuron, Vol. 81, No. 2, 22.01.2014, p. 314-320.

Research output: Contribution to journalArticle

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, vol. 81, no. 2, pp. 314-320. https://doi.org/10.1016/j.neuron.2013.11.011
Beppu, Kaoru ; Sasaki, Takuya ; Tanaka, Kenji ; Yamanaka, Akihiro ; Fukazawa, Yugo ; Shigemoto, Ryuichi ; Matsui, Ko. / Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. In: Neuron. 2014 ; Vol. 81, No. 2. pp. 314-320.
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