Rotenone aggravates PD-like pathology in A53T mutant human α-synuclein transgenic mice in an age-dependent manner.
Rotenone aggravates PD-like pathology in A53T mutant human α-synuclein transgenic mice in an age-dependent manner.
复制标题
鱼藤酮以年龄依赖性方式加重 A53T 突变人类 α-突触核蛋白转基因小鼠的 PD 样病理
DOI：
10.3389/fnagi.2022.842380
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
多种因素，如基因，环境和年龄参与发展帕金森病（PD）的病理。然而，各种因素如何相互作用导致PD仍不清楚。在这里，3个月和9个月大的hα-syn+ β/−小鼠用低剂量鱼藤酮治疗2个月，以探索强调PD发生中环境-基因-年龄相互作用的机制。我们已经检查了小鼠的行为以及大脑和肠道的PD样病理。结果表明，鱼藤酮对老年hα-syn+/-小鼠的运动功能和嗅觉功能损害较青年小鼠严重。鱼藤酮处理后，老年hα-syn+/-小鼠黑质致密部多巴胺能神经元丢失率高于年轻小鼠。鱼藤酮处理2个月后，hα-syn+/-小鼠的SNc中hα-syn+/-的表达增加。此外，在用鱼藤酮处理的老年hα-syn+/-小鼠的SNc中，活化的小胶质细胞数量增加，并伴随着炎性细胞因子即TNF-α和IL-18在中脑中的高表达。同时发现鱼藤酮治疗后，hα-syn阳性颗粒沉积于肠壁，肠道菌群和派尔集合淋巴结T淋巴细胞亚群发生变化，肠粘膜通透性增加。此外，这些现象与年龄有关。这些结果表明，鱼藤酮加重PD样病变，并以年龄依赖性方式影响人α-syn+/-转基因小鼠的脑和肠道。
Multiple factors such as genes, environment, and age are involved in developing Parkinson’s disease (PD) pathology. However, how various factors interact to cause PD remains unclear. Here, 3-month and 9-month-old hα-syn+/− mice were treated with low-dose rotenone for 2 months to explore the mechanisms that underline the environment–gene–age interaction in the occurrence of PD. We have examined the behavior of mice and the PD-like pathologies of the brain and gut. The present results showed that impairments of the motor function and olfactory function were more serious in old hα-syn+/– mice with rotenone than that in young mice. The dopaminergic neuron loss in the SNc is more in old hα-syn+/– mice with rotenone than in young mice. Expression of hα-syn+/– is increased in the SNc of hα-syn+/– mice following rotenone treatment for 2 months. Furthermore, the number of activated microglia cells increased in SNc and accompanied the high expression of inflammatory cytokines, namely, TNF-α and IL-18 in the midbrain of old hα-syn+/– mice treated with rotenone. Meanwhile, we found that after treatment with rotenone, hα-syn positive particles deposited in the intestinal wall, intestinal microflora, and T lymphocyte subtypes of Peyer’s patches changed, and intestinal mucosal permeability increased. Moreover, these phenomena were age-dependent. These findings suggested that rotenone aggravated the PD-like pathologies and affected the brain and gut of human α-syn+/– transgenic mice in an age-dependent manner.