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Neuron. 2014 Jan 22;81(2):314-20. doi: 10.1016/j.neuron.2013.11.011.

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

Author information

1
Division of Cerebral Structure, National Institute for Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan; Department of Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan.
2
Division of Cerebral Structure, National Institute for Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan.
3
Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160-8582, Japan.
4
Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
5
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
6
Division of Cerebral Structure, National Institute for Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan; Department of Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan; IST Austria, 3400 Klosterneuburg, Austria.
7
Division of Cerebral Structure, National Institute for Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan; Department of Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan; Division of Interdisciplinary Medical Science, Center for Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: matsui@med.tohoku.ac.jp.

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.

PMID:
24462096
DOI:
10.1016/j.neuron.2013.11.011
[Indexed for MEDLINE]
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