Sonogenetic-Based Neuromodulation for the Amelioration of Parkinson's Disease

被引：35

作者：

Fan, Ching-Hsiang ^{[1
,2
]}

Wei, Kuo-Chen ^{[3
,4
,5
]}

Chiu, Nai-Hua ^{[6
]}

Liao, En-Chi ^{[7
]}

Wang, Hsien-Chu ^{[8
]}

Wu, Ruo-Yu ^{[9
]}

Ho, Yi-Ju ^{[10
]}

Chan, Hong-Lin ^{[7
]}

Wang, Tsung-Shing Andrew ^{[9
]}

Huang, Ying-Zu ^{[11
,12
,13
]}

Hsieh, Tsung-Hsun ^{[13
,14
,15
]}

Lin, Chin-Hsien ^{[16
]}

Lin, Yu-Chun ^{[8
,17
]}

Yeh, Chih-Kuang ^{[10
]}

机构：

[1] Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 70101, Taiwan

[2] Natl Cheng Kung Univ, Med Device Innovat Ctr, Tainan 70101, Taiwan

[3] New Taipei Municipal TuCheng Hosp, New Taipei 236017, Taiwan

[4] Chang Gung Mem Hosp Linkou, Dept Neurosurg, Taoyuan 33305, Taiwan

[5] Chang Gung Univ, Taoyuan 33305, Taiwan

[6] Natl Tsing Hua Univ, Inst Nucl Engn & Sci, Hsinchu 30013, Taiwan

[7] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Dept Med Sci, Hsinchu 30013, Taiwan

[8] Natl Tsing Hua Univ, Inst Mol Med, Hsinchu 30013, Taiwan

[9] Natl Taiwan Univ, Dept Chem, Taipei 106319, Taiwan

[10] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu 30013, Taiwan

[11] Chang Gung Mem Hosp, Neurosci Res Ctr, Hlth Aging Res Ctr, Taoyuan 33305, Taiwan

[12] Chang Gung Mem Hosp, Dept Neurol, Taoyuan 33305, Taiwan

[13] Chang Gung Univ, Coll Med, Taoyuan 33305, Taiwan

[14] Chang Gung Mem Hosp, Sch Phys Therapy, Hlth Aging Res Ctr, Taoyuan 33305, Taiwan

[15] Chang Gung Mem Hosp, Neurosci Res, Taoyuan 33305, Taiwan

[16] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Neurol, Taipei 106319, Taiwan

[17] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 30013, Taiwan

来源：

NANO LETTERS | 2021年 / 21卷 / 14期

关键词：

sonogenetics; ultrasound; Parkinson's disease; dopaminergic neuron; ultrasound-sensing protein; INTENSITY PULSED ULTRASOUND; BLOOD-BRAIN-BARRIER; FOCUSED ULTRASOUND; L-DOPA; TARGETED DELIVERY; RANDOMIZED-TRIAL; MOUSE MODEL; RAT MODEL; THALAMOTOMY; MICROBUBBLES;

D O I：

10.1021/acs.nanolett.1c00886

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Sonogenetics is a promising strategy allowing the noninvasive and selective activation of targeted neurons in deep brain regions; nevertheless, its therapeutic outcome for neurodegeneration diseases that need long-term treatment remains to be verified. We previously enhanced the ultrasound (US) sensitivity of targeted cells by genetic modification with an engineered auditorysensing protein, mPrestin (N7T, N308S). In this study, we expressed mPrestin in the dopaminergic neurons of the substantia nigra in Parkinson's disease (PD) mice and used 0.5 MHz US for repeated and localized brain stimulation. The mPrestin expression in dopaminergic neurons persisted for at least 56 days after a single shot of adeno-associated virus, suggesting that the period of expression was long enough for US treatment in mice. Compared to untreated mice, US stimulation ameliorated the dopaminergic neurodegeneration 10-fold and mitigated the PD symptoms of the mice 4-fold, suggesting that this sonogenetic strategy has the clinical potential to treat neurodegenerative diseases.

引用

页码：5967 / 5976

页数：10

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