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

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...

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Autores principales:	Jormay Lim, Hsiao-Hsin Tai, Wei-Hao Liao, Ya-Cherng Chu, Chen-Ming Hao, Yueh-Chun Huang, Cheng-Han Lee, Shao-Shien Lin, Sherry Hsu, Ya-Chih Chien, Dar-Ming Lai, Wen-Shiang Chen, Chih-Cheng Chen, Jaw-Lin Wang
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	mechanoreceptor ultrasound micropipette neuron calcium signal ASIC1a Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ac260d264ce0451eaf621448a1f84dd9
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spelling	oai:doaj.org-article:ac260d264ce0451eaf621448a1f84dd92021-11-23T13:03:29ZASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain10.7554/eLife.616602050-084Xe61660https://doaj.org/article/ac260d264ce0451eaf621448a1f84dd92021-09-01T00:00:00Zhttps://elifesciences.org/articles/61660https://doaj.org/toc/2050-084XAccumulating 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.Jormay LimHsiao-Hsin TaiWei-Hao LiaoYa-Cherng ChuChen-Ming HaoYueh-Chun HuangCheng-Han LeeShao-Shien LinSherry HsuYa-Chih ChienDar-Ming LaiWen-Shiang ChenChih-Cheng ChenJaw-Lin WangeLife Sciences Publications Ltdarticlemechanoreceptorultrasoundmicropipetteneuroncalcium signalASIC1aMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mechanoreceptor ultrasound micropipette neuron calcium signal ASIC1a Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	mechanoreceptor ultrasound micropipette neuron calcium signal ASIC1a Medicine R Science Q Biology (General) QH301-705.5 Jormay Lim Hsiao-Hsin Tai Wei-Hao Liao Ya-Cherng Chu Chen-Ming Hao Yueh-Chun Huang Cheng-Han Lee Shao-Shien Lin Sherry Hsu Ya-Chih Chien Dar-Ming Lai Wen-Shiang Chen Chih-Cheng Chen Jaw-Lin Wang ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
description	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.
format	article
author	Jormay Lim Hsiao-Hsin Tai Wei-Hao Liao Ya-Cherng Chu Chen-Ming Hao Yueh-Chun Huang Cheng-Han Lee Shao-Shien Lin Sherry Hsu Ya-Chih Chien Dar-Ming Lai Wen-Shiang Chen Chih-Cheng Chen Jaw-Lin Wang
author_facet	Jormay Lim Hsiao-Hsin Tai Wei-Hao Liao Ya-Cherng Chu Chen-Ming Hao Yueh-Chun Huang Cheng-Han Lee Shao-Shien Lin Sherry Hsu Ya-Chih Chien Dar-Ming Lai Wen-Shiang Chen Chih-Cheng Chen Jaw-Lin Wang
author_sort	Jormay Lim
title	ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
title_short	ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
title_full	ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
title_fullStr	ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
title_full_unstemmed	ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
title_sort	asic1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/ac260d264ce0451eaf621448a1f84dd9
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ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

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