Low-intensity pulsed ultrasound modulates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Zihao Liu,
Huan Zhang,
Kaili Lu,
Li Chen,
Yueqi Zhang,
Zhouwei Xu,
Hongsheng Zhou,
Junfeng Sun,
Mengyang Xu,
Qi Ouyang,
Garth J. Thompson,
Yi Yang,
Ni Su,
Xiaojun Cai,
Li Cao,
Yuwu Zhao,
Lixian Jiang,
Yuanyi Zheng,
Xiaojie Zhang
Affiliations
Zihao Liu
Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Huan Zhang
Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Kaili Lu
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Li Chen
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Yueqi Zhang
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Zhouwei Xu
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Hongsheng Zhou
Institute of Advanced Ultrasonic Technology, National Innovation Center par Excellence, Shanghai 201203, China
Junfeng Sun
Shanghai Med-X Engineering Research Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
Mengyang Xu
iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Qi Ouyang
iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Garth J. Thompson
iHuman Institute, ShanghaiTech University, Shanghai 201210, China
Yi Yang
Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Ni Su
Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Xiaojun Cai
Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Li Cao
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China; Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform, Shanghai 200233, China
Yuwu Zhao
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China
Lixian Jiang
Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China; Corresponding author
Yuanyi Zheng
Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China; Corresponding author
Xiaojie Zhang
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai 200233, China; Corresponding author
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1G93A mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.
