Acidification of extracellular space occurs in brain ischemia. This acidification is one important contributor to ischemia-induced neuronal injury. Current literature emphasizes an injurious role of acidosis, mediated mostly by the acid-sensing ion channels in ischemia. The current proposal investigates a novel signaling pathway mediated by ovarian cancer G protein-coupled receptor 1 (OGR1), an acid-sensitive G protein coupled receptor. With the OGR1 null mice and organotypic hippocampal slices, we will test the hypothesis that activating the OGR1 pathway attenuates acidosis- and ischemic-induced neuronal injury. The proposed research will uncover an unexpected neuroprotective aspect of acidosis. The results will reveal a biphasic (pro-survival vs. pro-injury) picture of acidosis in neuronal survival, and will be critical for future therapeutic interventions in stroke and other neurological diseases that reduces brain pH.
Extracellular acidification occurs in ischemia, multiple sclerosis, epilepsy and various neurodegenerative diseases. This project investigates a novel signaling pathway in response to pH reduction, and will generate information that is important for understanding the etiology of multiple neurological diseases.
| Xu, Yuanyuan; Jiang, Yu-Qing; Li, Ce et al. (2018) Human ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a. FASEB J 32:3832-3843 |
| Jiang, Yu-Qing; Zha, Xiang-Ming (2017) miR-149 reduces while let-7 elevates ASIC1a expression in vitro. Int J Physiol Pathophysiol Pharmacol 9:147-152 |
| Jiang, Nan; Wu, Junjun; Leng, Tiandong et al. (2017) Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury. J Cereb Blood Flow Metab 37:528-540 |
| Wu, Junjun; Leng, Tiandong; Jing, Lan et al. (2016) Two di-leucine motifs regulate trafficking and function of mouse ASIC2a. Mol Brain 9:9 |
| Wu, Junjun; Xu, Yuanyuan; Jiang, Yu-Qing et al. (2016) ASIC subunit ratio and differential surface trafficking in the brain. Mol Brain 9:4 |
