Medical College of China Three Gorges University, Yichang, China.
Geriatr Gerontol Int. 2021 Jan;21(1):85-93. doi: 10.1111/ggi.13882. Epub 2020 Nov 27.
The enteric nervous system degenerates gradually with age, and α-synuclein (α-syn) is a suitable marker of enteric nervous system degeneration, which is intimately related with endoplasmic reticulum stress and unfolded protein response (UPR ). Saponins from Panax japonicus (SPJ) have obvious protective effects on neurons in several degenerative disease models. Here, the study was designed to investigate whether SPJ could reverse the neuron degeneration through regulating the UPR in the colon myenteric plexus of aging rats.
Aging rats had been treated with SPJ for 6 months since they were aged 18 months. Then, the colon samples were collected and neuron morphology in the myenteric plexus was observed. Immunohistochemistry staining was used to detect the expressions of NeuN, α-syn, GRP78 and three different UPR branches. Double immunofluorescence was used to determine the co-localization of α-syn and NeuN, GRP78 and NeuN.
Neurons degenerated in the colon myenteric plexus of aging rats, but co-localization of α-syn and NeuN increased. In addition, both the expressions of GRP78 and three UPR branch signaling pathway proteins decreased in the colon myenteric plexus of aging rats. Treatment of SPJ almost alleviated the above effects in aging rats, except for ATF6.
SPJ could reverse the neuron loss caused by accumulation of α-syn in the myenteric plexus of colon in aging rats, which is potentially associated with increased GRP78 and most URP changes. Geriatr Gerontol Int 2021; 21: 85-93.
肠神经系统会随着年龄逐渐退化,而α-突触核蛋白(α-syn)是肠神经系统退化的一个合适标志物,它与内质网应激和未折叠蛋白反应(UPR)密切相关。人参属植物(Panax japonicus)皂苷(SPJ)对几种退行性疾病模型中的神经元具有明显的保护作用。本研究旨在探讨 SPJ 是否可以通过调节衰老大鼠结肠肌间神经丛中的 UPR 来逆转神经元退化。
18 月龄的大鼠开始用 SPJ 治疗 6 个月,然后收集结肠样本,观察肌间神经丛中的神经元形态。免疫组织化学染色用于检测 NeuN、α-syn、GRP78 和三个不同 UPR 分支的表达。双免疫荧光用于确定 α-syn 和 NeuN、GRP78 和 NeuN 的共定位。
衰老大鼠结肠肌间神经丛中的神经元退化,但 α-syn 和 NeuN 的共定位增加。此外,衰老大鼠结肠肌间神经丛中 GRP78 和三个 UPR 分支信号通路蛋白的表达均降低。SPJ 处理几乎缓解了衰老大鼠的上述作用,除了 ATF6。
SPJ 可逆转衰老大鼠结肠肌间神经丛中 α-syn 积累引起的神经元丢失,这可能与 GRP78 和大多数 URP 变化增加有关。老年医学与老年病学杂志 2021; 21: 85-93。