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

Ching Hsiang Fan, Kuo Chen Wei, Nai Hua Chiu, En Chi Liao, Hsien Chu Wang, Ruo Yu Wu, Yi-Ju Ho, Hong Lin Chan, Tsung Shing Andrew Wang, Ying Zu Huang, Tsung Hsun Hsieh, Chin Hsien Lin, Yu Chun Lin*, Chih Kuang Yeh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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 auditory-sensing 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.

Original languageEnglish
Pages (from-to)5967-5976
Number of pages10
JournalNano letters
Volume21
Issue number14
DOIs
StatePublished - 28 Jul 2021

Keywords

  • dopaminergic neuron
  • Parkinson's disease
  • sonogenetics
  • ultrasound
  • ultrasound-sensing protein

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