ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

eLife

Hsiao-Hsin Tai¹  Yueh-Chun Huang¹  Sherry Hsu¹  Jaw-Lin Wang¹  Jormay Lim¹  Chen-Ming Hao¹  Ya-Cherng Chu¹  Wei-Hao Liao²  Wen-Shiang Chen²  Dar-Ming Lai³  Shao-Shien Lin³  Ya-Chih Chien⁴  Cheng-Han Lee⁴  Chih-Cheng Chen⁴ 

[1] Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan;Department of Physical Medicine and Rehabilitation, National Taiwan Hospital University, Taipei, Taiwan;Department of Surgery, National Taiwan Hospital University, Taipei, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;

关键词: mechanoreceptor;    ultrasound;    micropipette;    neuron;    calcium signal;    ASIC1a;   

DOI  :  10.7554/eLife.61660

来源: DOAJ

【 摘 要 】

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.

【 授权许可】

Unknown