Modulation of GABAergic neurons in acute epilepsy using sonogenetics

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2024-11-23 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

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引用次数: 0

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.

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利用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紊乱引起的神经系统疾病，传统的治疗方法包括手术、药物治疗以及神经调控技术，如脑深部刺激和迷走神经刺激。然而，这些方法往往受到侵入性、脱靶效应和分辨率低的限制。我们提出了一种非侵入性替代方法，即在戊四唑诱导的大鼠模型中，利用声遗传学技术，通过工程听觉感应蛋白 mPrestin (N7T, N308S) 选择性地刺激杏仁核中的γ-氨基丁酸（GABA）能神经元。用0.5兆赫的经颅超声波激活GABA能神经元，可将癫痫样活动调控50%。电生理学记录证实了有效的神经调节和持续的癫痫发作抑制，直至治疗后 60 分钟，且无组织损伤、炎症或细胞凋亡。这种声遗传学方法通过靶向 GABA 能神经元，为癫痫治疗提供了一种前景广阔的安全方法。

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.