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Modulation of GABAergic neurons in acute epilepsy using sonogenetics.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-11-16 , DOI: 10.1016/j.jconrel.2024.11.029
Thi-Nhan Phan,Ching-Hsiang Fan,Hsien-Chu Wang,Hao-Li Liu,Yu-Chun Lin,Chih-Kuang Yeh

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.

中文翻译:


使用超声遗传学调节急性癫痫中的 GABA 能神经元。



癫痫是一种由超同步神经干扰引起的神经系统疾病,传统上通过手术、药物治疗和神经调控技术(如脑深部刺激和迷走神经刺激)进行治疗。然而,这些方法通常受到侵入性、脱靶效应和较差分辨率的限制。我们提出了一种利用声遗传学的无创替代方案,通过工程听觉感应蛋白 mPrestin (N7T, N308S) 在戊烯四唑诱导的大鼠模型中选择性地刺激杏仁核中的 γ-氨基丁酸 (GABA) 能神经元。用 0.5 MHz 经颅超声超声处理诱导的 GABA 能神经元激活可以调节 50% 的癫痫样活动。电生理记录证实,治疗后长达 60 分钟的有效神经调控和持续性癫痫发作抑制,无组织损伤、炎症或细胞凋亡。这种声原方法通过靶向 GABA 能神经元为癫痫管理提供了一种有前途、安全的方法。
更新日期:2024-11-16
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