半帕金森病大鼠在意志步态和冻结时的小脑活动

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-10-25 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae246
Valerie DeAngelo, Arianna Gehan, Siya Paliwal, Katherine Ho, Justin D Hilliard, Chia-Han Chiang, Jonathan Viventi, George C McConnell
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引用次数: 0

摘要

帕金森病是一种神经退行性疾病,晚期患者会出现步态功能障碍。单侧 6-羟基多巴胺毒素诱导模型是研究最多的帕金森病动物模型,该模型再现了黑质紧实部多巴胺损失>68%后的步态功能障碍。半帕金森病大鼠的神经活动与步态功能障碍和多巴胺能细胞缺失的相关程度尚不清楚。在这篇文章中,我们报告了单侧多巴胺耗竭对小脑蚓部活动的影响,这种影响是在跑道上行走和冻结时使用显微皮层电图进行的。在向内侧前脑束注入 6-羟基多巴胺或对照品(n = 20)14、21 和 28 天后,对 4 至 5 个月大的 6-羟基多巴胺和假缺损大鼠的步态和神经活动进行了测量。14 天时,6-羟基多巴胺大鼠的步态障碍与假大鼠不同(P < 0.05)。6-羟基多巴胺大鼠的步态障碍在21天和28天时有所改善,但奔跑速度在28天时有所下降(P = 0.018)。假缺损大鼠在任何时间点的步态障碍均无差异。半帕金森病大鼠在21天时小脑蚓部表现出过度活动(P < 0.05),但在14天和28天时没有表现出过度活动,而且在第VIa、VIb和VIc小叶的冻结期活动减少(P < 0.05)。这些结果表明,多巴胺能细胞缺失会在脑损伤后21天引起病理性小脑活动,并表明来自完整半球的代偿机制有助于在28天时使小脑活动恢复正常。冻结过程中小脑振荡活动的减少可能表明帕金森病患者在步态冻结过程中神经系统发生了变化,这使得该区域成为生物标记物检测的潜在位置。虽然单侧 6-羟基多巴胺模型表现出的步态障碍与帕金森病的临床表现相似,但要了解小脑蚓部在帕金森病中的作用,还需要对双侧多巴胺缺失的动物模型进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cerebellar activity in hemi-parkinsonian rats during volitional gait and freezing.

Parkinson's disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-hydroxydopamine toxin-induced model is the most studied animal model of Parkinson's disease, which reproduces gait dysfunction after >68% dopamine loss in the substantia nigra pars compacta. The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and dopaminergic cell loss is not clear. In this article, we report the effects of unilateral dopamine depletion on cerebellar vermis activity using micro-electrocorticography during walking and freezing on a runway. Gait and neural activity were measured in 6-hydroxydopamine- and sham-lesioned rats aged between 4 and 5 months at 14, 21 and 28 days after infusion of 6-hydroxydopamine or control vehicle into the medial forebrain bundle (n = 20). Gait deficits in 6-hydroxydopamine rats were different from sham rats at 14 days (P < 0.05). Gait deficits in 6-hydroxydopamine rats improved at 21 and 28 days except for run speed, which decreased at 28 days (P = 0.018). No differences in gait deficits were observed in sham-lesioned rats at any time points. Hemi-parkinsonian rats showed hyperactivity in the cerebellar vermis at 21 days (P < 0.05), but not at 14 and 28 days, and the activity was reduced during freezing epochs in Lobules VIa, VIb and VIc (P < 0.05). These results suggest that dopaminergic cell loss causes pathological cerebellar activity at 21 days post-lesion and suggest that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28 days. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in patients with Parkinson's disease making this region a potential location for biomarker detection. Although the unilateral 6-hydroxydopamine model presents gait deficits that parallel clinical presentations of Parkinson's disease, further studies in animal models of bilateral dopamine loss are needed to understand the role of the cerebellar vermis in Parkinson's disease.

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