美国卡内基梅隆大学Aryn Gittis研究组的最新研究揭示了特定人群的神经调节延长了深部脑刺激的治疗效果。该项研究成果发表在2021年10月8日出版的《科学》上。

他们使用突触差异来激发表达小清蛋白的苍白球外部 (GPe)神经元，并使用短暂的电刺激同时抑制表达 lim-homeobox-6 的 GPe 神经元。在多巴胺耗尽 (DD)小鼠中，受回路启发的深部脑刺激 (DBS)提供了远远超过传统 DBS 诱导的持久治疗益处，在刺激后持续数小时。这些结果确立了将回路结构知识转化为可翻译治疗方法的可行性。

研究人员表示，神经系统疾病的症状是由于神经回路的功能障碍而出现的，其扩散和交织的结构对提供治疗提出了严峻的挑战。DBS可迅速改善帕金森病症状，但不能区分神经元回路，如果停止刺激，其效果会迅速减弱。最近的研究结果表明，对 GPe中不同神经元亚群的光遗传学操作为DD小鼠提供了持久的治疗效果。

附：英文原文

Title: Population-specific neuromodulation prolongs therapeutic benefits of deep brain stimulation

Author: Teresa A. Spix, Shruti Nanivadekar, Noelle Toong, Irene M. Kaplow, Brian R. Isett, Yazel Goksen, Andreas R. Pfenning, Aryn H. Gittis

Issue&Volume: 2021-10-08

Abstract: Symptoms of neurological diseases emerge through the dysfunction of neural circuits whose diffuse and intertwined architectures pose serious challenges for delivering therapies. Deep brain stimulation (DBS) improves Parkinson’s disease symptoms acutely but does not differentiate between neuronal circuits, and its effects decay rapidly if stimulation is discontinued. Recent findings suggest that optogenetic manipulation of distinct neuronal subpopulations in the external globus pallidus (GPe) provides long-lasting therapeutic effects in dopamine-depleted (DD) mice. We used synaptic differences to excite parvalbumin-expressing GPe neurons and inhibit lim-homeobox-6–expressing GPe neurons simultaneously using brief bursts of electrical stimulation. In DD mice, circuit-inspired DBS provided long-lasting therapeutic benefits that far exceeded those induced by conventional DBS, extending several hours after stimulation. These results establish the feasibility of transforming knowledge of circuit architecture into translatable therapeutic approaches.

DOI: abi7852

Source: https://www.science.org/doi/10.1126/science.abi7852