ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1582970
Selective blockade of Acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection
Provisionally accepted
- 1Department of Neurology, The First Hospital of Jilin University, Changchun, China., changchun, China
- 2Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
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Acid-sensing ion channel 1a (ASIC1a) is the only member of the ASIC family where Ca 2+ osmosis has been reported, which is highly expressed in neurons of the central nervous system. This study aimed to investigate whether ASIC1a is trafficked to the plasma membrane and regulated by Rho/ROCK and PI3K signaling pathways in temporal lobe epilepsy (TLE). Besides, further research is required to determine whether selective ASIC1a blockade is a viable therapeutic strategy for TLE.The localization and expression levels of ASIC1 and mRNA levels of ASIC1a were detected when the Rho/ROCK and PI3K signaling pathways were activated and inhibited in glutamate (Glu)-induced cell. Meanwhile, we analyzed the location and expression of ASIC1 using Western blotting and immunofluorescence in brain tissue samples of TLE patients, Kainic acid rats and Glu-induced primary hippocampal neurons. There are currently no specific ASIC1a antibody available, so ASIC1 antibody was used in this study as in previous studies. Furthermore, we evaluated the HT22 cell survival rate, mitochondrial damage, apoptosis and autophagy to examine whether selective blocking ASIC1a(PcTx1) could play a neuroprotective role.Firstly, the Rho/ROCK and PI3K signaling pathways provide an effect on regulating the expression and localization of ASIC1, especially on the mRNA levels of ASIC1a in the Glu-induced HT22 cell injury model. Secondly, the high expression of ASIC1 in epilepsy patients was verified in all three samples, and the phenomenon of its transport from cytoplasm to cell membrane/mitochondria was confirmed. Finally, although ASIC1 has a limited epileptogenic effect in the acute phase of epilepsy in vivo, selective blockade of ASIC1a using PcTx1 provided significant hippocampal neuroprotection as well as reduced mitochondrial damage, apoptosis, and cellular autophagy in vitro.This study is a systematic report concerning ASIC1a in temporal lobe epilepsy, including in vivo and in vitro experiments concerning both the acute and chronic phases. It provides foundational research for proposing ASIC1a as a new target for epilepsy treatment.
Keywords: ASIC1a, Temporal Lobe Epilepsy, Neuroprotection, Hippocampus, Rho/ROCK, PI3K
Received: 25 Feb 2025; Accepted: 29 May 2025.
Copyright: © 2025 Li, Cheng, Ma, Li, Zhao, Jiang and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiaai Li, Department of Neurology, The First Hospital of Jilin University, Changchun, China., changchun, China
Hongmei Meng, Department of Neurology, The First Hospital of Jilin University, Changchun, China., changchun, China
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