Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
Genes (Basel). 2021 Mar 10;12(3):392. doi: 10.3390/genes12030392.
Parkinson's disease (PD) is a prevalent motor disease caused by the accumulation of mutated α-synuclein (α-Syn); however, its early stages are also characterized by non-motor symptoms, such as olfactory loss, cognitive decline, depression, and anxiety. The therapeutic effects of environmental enrichment (EE) on motor recovery have been reported, but its effects on non-motor symptoms remain unclear. Herein, we reveal the beneficial effects of EE on PD-related non-motor symptoms and changes in synaptic plasticity in the nucleus accumbens. To investigate its therapeutic effects in the early phase of PD, we randomly assigned eight-month-old mice overexpressing human A53T (hA53T) α-Syn to either the EE or standard condition groups for two months. Next, we performed behavioral tests and biochemical and histological analyses at 10 months of age. EE significantly alleviated locomotor hyperactivity and anxiety during the early stages of PD. It normalized the levels of tyrosine hydroxylase, phosphorylated and oligomeric α-Syn, and soluble -ethylmaleimide-sensitive factor attachment protein receptor complex-forming proteins, including synaptosomal-associated protein, 25 kDa, syntaxin1, and vesicle-associated membrane protein 2 (VAMP2). Moreover, the interactions between VAMP2 and pSer129 α-Syn were markedly reduced following EE. The restoration of synaptic vesicle transportation status may underlie the neuroprotective effects of EE in hA53T α-Syn mice.
帕金森病（PD）是一种常见的运动疾病，由突变的α-突触核蛋白（α-Syn）积累引起；然而，其早期阶段也以非运动症状为特征，如嗅觉丧失、认知能力下降、抑郁和焦虑。环境富集（EE）对运动功能恢复的治疗效果已经有报道，但它对非运动症状的影响仍不清楚。在此，我们揭示了 EE 对 PD 相关非运动症状和伏隔核突触可塑性变化的有益影响。为了研究其在 PD 早期阶段的治疗效果，我们将 8 个月大的过度表达人 A53T（hA53T）α-Syn 的小鼠随机分为 EE 或标准条件组，进行为期两个月的干预。然后，我们在 10 个月大时进行行为测试和生化及组织学分析。EE 显著缓解了 PD 早期的运动过度活跃和焦虑。它使酪氨酸羟化酶、磷酸化和寡聚化 α-Syn 以及可溶性乙基maleimide 敏感因子附着蛋白受体复合物形成蛋白（包括突触相关蛋白 25kDa、突触素 1 和囊泡相关膜蛋白 2（VAMP2））的水平正常化。此外，EE 后 VAMP2 与 pSer129 α-Syn 的相互作用明显减少。突触囊泡运输状态的恢复可能是 EE 在 hA53T α-Syn 小鼠中发挥神经保护作用的基础。
