Institute of Geriatric Neurology, Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Nutrition and Diseases, Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Institute of Geriatric Neurology, Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Neurology, Lishui Hospital of Zhejiang University (the Central Hospital of Lishui), Lishui, Zhejiang, China.
J Nutr. 2023 Jan;153(1):167-175. doi: 10.1016/j.tjnut.2022.11.006. Epub 2022 Dec 21.
Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD.
The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms.
Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 μg/g) or Zn deficient (ZnD; <5 μg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test.
Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (P = 0.012, P = 0.014), reduced total distance traveled (P < 0.001, P = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (P < 0.001, P = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation.
Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.
循环锌（Zn）浓度在帕金森病（PD）患者中低于正常水平。尚不清楚锌缺乏是否会增加 PD 的易感性。
本研究旨在探讨饮食性 Zn 缺乏对 PD 小鼠模型行为和多巴胺能神经元的影响，并探讨潜在机制。
8-10 周龄雄性 C57BL/6J 小鼠用 Zn 充足（ZnA；30μg/g）或 Zn 缺乏（ZnD；<5μg/g）饮食喂养，整个实验期间均给予相应饮食。6 周后，用 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）注射建立 PD 模型。对照组注射生理盐水。因此，形成了 4 组（生理盐水-ZnA、生理盐水-ZnD、MPTP-ZnA 和 MPTP-ZnD）。实验持续 13 周。进行了旷场试验、旋转棒试验、免疫组织化学和 RNA 测序。采用 t 检验、双因素方差分析或 Kruskal-Wallis 检验进行数据分析。
MPTP 和 ZnD 饮食处理均导致血液 Zn 浓度显著降低（P=0.012，P=0.014），总行进距离减少（P<0.001，P=0.031），并影响黑质多巴胺能神经元的变性（P<0.001，P=0.020）。在 MPTP 处理的小鼠中，ZnD 饮食使总行进距离减少 22.4%（P=0.026），跌落潜伏期减少 49.9%（P=0.026），多巴胺能神经元减少 59.3%（P=0.002），与 ZnA 饮食相比。RNA 测序分析显示，ZnD 组小鼠黑质中共有 301 个差异表达基因（156 个上调；145 个下调）。这些基因参与了许多过程，包括蛋白质降解、线粒体完整性和α-突触核蛋白聚集。
Zn 缺乏加重 PD 小鼠的运动障碍。我们的结果支持之前的临床观察结果，并表明适当的 Zn 补充可能对 PD 有益。
