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


Author(s): Beppu, Kaoru; Sasaki, Takuya; Tanaka, Kenji F; Yamanaka, Akihiro; Fukazawa, Yugo; Shigemoto, Ryuichi; Matsui, Ko
Article Title: Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage
Affiliation IST Austria
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.
Journal Title: Neuron
Volume: 81
Issue 2
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2014-01-22
Start Page: 314
End Page: 320
DOI: 10.1016/j.neuron.2013.11.011
Notes: This work was supported by grants from Grant-in-Aid for Scientific Research on Innovative Areas “Mesoscopic Neurocircuitry” and “Comprehensive Brain Science Network” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) to K.M. (25115729), A.Y. (23115103), and Y.F. (23115520), Grant-in-Aid for Young Scientists (A) from MEXT to K.M. (25702054) and K.F.T. (23680042), Takeda Science Foundation to K.M., K.F.T., and A.Y., and Grant-in-Aid for Scientific Research (B) from MEXT to A.Y. (23300142).
Open access: no