Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
Nat Commun. 2021 Feb 26;12(1):1295. doi: 10.1038/s41467-021-21417-8.
Deep brain stimulation (DBS) relieves motor dysfunction in Parkinson's disease, and other movement disorders. Here, we demonstrate the potential benefits of DBS in a model of ataxia by targeting the cerebellum, a major motor center in the brain. We use the Car8 mouse model of hereditary ataxia to test the potential of using cerebellar nuclei DBS plus physical activity to restore movement. While low-frequency cerebellar DBS alone improves Car8 mobility and muscle function, adding skilled exercise to the treatment regimen additionally rescues limb coordination and stepping. Importantly, the gains persist in the absence of further stimulation. Because DBS promotes the most dramatic improvements in mice with early-stage ataxia, we postulated that cerebellar circuit function affects stimulation efficacy. Indeed, genetically eliminating Purkinje cell neurotransmission blocked the ability of DBS to reduce ataxia. These findings may be valuable in devising future DBS strategies.
脑深部电刺激（DBS）可缓解帕金森病和其他运动障碍的运动功能障碍。在这里，我们通过靶向大脑中的主要运动中心小脑，展示了 DBS 在共济失调模型中的潜在益处。我们使用遗传性共济失调的 Car8 小鼠模型来测试小脑核 DBS 加体力活动恢复运动的潜力。虽然单独进行低频小脑 DBS 可改善 Car8 的活动能力和肌肉功能，但将熟练运动添加到治疗方案中还可挽救肢体协调和步态。重要的是，在没有进一步刺激的情况下，这些收益仍然存在。由于 DBS 可使早期共济失调的小鼠获得最显著的改善，因此我们推测小脑回路功能会影响刺激效果。实际上，通过基因消除浦肯野细胞的神经传递，阻断了 DBS 减轻共济失调的能力。这些发现对于设计未来的 DBS 策略可能具有重要价值。
