Modulation of GABAergic neurons in acute epilepsy using sonogenetics

Thi-Nhan Phan; Ching-Hsiang Fan; Hsien-Chu Wang; Hao-Li Liu; Yu-Chun Lin; Chih-Kuang Yeh

doi:10.1016/j.jconrel.2024.11.029

Modulation of GABAergic neurons in acute epilepsy using sonogenetics

J Control Release. 2024 Nov 23:377:341-353. doi: 10.1016/j.jconrel.2024.11.029. Online ahead of print.

Authors

Thi-Nhan Phan¹, Ching-Hsiang Fan², Hsien-Chu Wang³, Hao-Li Liu⁴, Yu-Chun Lin⁵, Chih-Kuang Yeh⁶

Affiliations

¹ Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
² Department of Biomedical Engineering, National Cheng Kung University, Tainan 701401, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan 701401, Taiwan.
³ Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.
⁴ Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan.
⁵ Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: ycl@life.nthu.edu.tw.
⁶ Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: ckyeh@mx.nthu.edu.tw.

PMID: 39557217
DOI: 10.1016/j.jconrel.2024.11.029

Abstract

Epilepsy, a neurological disorder caused by hypersynchronous neural disturbances, has traditionally been treated with surgery, pharmacotherapy, and neuromodulation techniques such as deep brain stimulation and vagus nerve stimulation. However, these methods are often limited by invasiveness, off-target effects, and poor resolution. We present a noninvasive alternative utilizing sonogenetics to selectively stimulate γ-aminobutyric acid (GABA)ergic neurons in the amygdala through engineered auditory-sensing protein, mPrestin (N7T, N308S), in a pentylenetetrazole-induced rat model. Activation of GABAergic neurons induced by the sonication with 0.5-MHz transcranial ultrasound can modulate epileptiform activity by 50 %. Electrophysiological recordings confirmed effective neuromodulation and persistent seizure suppression up to 60 min post-treatment without tissue damage, inflammation, or apoptosis. This sonogenetic approach offers a promising, safe method for epilepsy management by targeting GABAergic neurons.

Keywords: Epilepsy seizures; GABAergic neuron; Neuromodulation; Sonogenetics; Ultrasound.