Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury.

Abstract

Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region-specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid-activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain.

• Authors: Nan Jiang, Junjun Wu, Tiandong Leng, Tao Yang, Yufan Zhou, Qian Jiang, Bin Wang, Youjia Hu, Yong-Hua Ji, Roger P Simon, Xiang-Ping Chu, Zhi-Gang Xiong, Xiang-Ming Zha
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 37 Issue 2 Pg. 528-540 (Feb 2017) ISSN: 1559-7016 [Electronic] United States
• PMID: 26861816 (Publication Type: Journal Article)

Chemical References

• ASIC2 protein, mouse
• Acid Sensing Ion Channels

Topics

• Acid Sensing Ion Channels (analysis, genetics, metabolism)
• Acidosis
• Animals
• Brain (metabolism, pathology)
• Brain Ischemia (genetics, metabolism, pathology)
• Gene Deletion
• Male
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Neurons (metabolism, pathology)
• Neuroprotection