中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (6): 1347-1353.doi: 10.4103/1673-5374.357902

• 原著:退行性病与再生 • 上一篇    下一篇

成纤维细胞生长因子13过表达可改善β淀粉样蛋白诱导的神经元损伤

  

  • 出版日期:2023-06-15 发布日期:2023-01-05

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage

Ruo-Meng Li, Lan Xiao, Ting Zhang, Dan Ren, Hong Zhu*   

  1. Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Hong Zhu, PhD, yellingu@163.com.

摘要:

尽管有研究表明,成纤维细胞生长因子13在阿尔茨海默病小鼠和患者大脑中表达下调,且其可在学习和记忆中发挥着重要作用,但其涉及的分子机制仍然不明。此次实验以双侧海马立体定向注射Aβ1-42建立阿尔茨海默病大鼠模型,双侧海马注射携带成纤维细胞生长因子13的慢病毒以过表达成纤维细胞生长因子13。可见阿尔茨海默病模型大鼠脑组织中成纤维细胞生长因子13表达下调。而成纤维细胞生长因子13过表达后,阿尔茨海默病大鼠模型学习记忆能力明显改善,脑组织中氧化应激相关标志物谷胱甘肽和超氧化物歧化酶、磷脂酰肌醇-3-激酶、AKT及糖原合成酶激酶3β磷酸化水平、抑凋亡因子BCL-2蛋白水平增加,而凋亡细胞数量、促凋亡因子BAX、Cleaved-caspase 3和β 淀粉样蛋白表达、Tau磷酸化、丙二醛、活性氧以及乙酰胆碱酯酶水平减少。且上述变化可被磷脂酰肌醇-3-激酶抑制剂LY294002所逆转。由此得出,成纤维细胞生长因子13过表达可通过激活磷脂酰肌醇-3-激酶/AKT/糖原合成酶激酶3β信号通路,改善阿尔茨海默病大鼠模型中大脑神经元损伤。

https://orcid.org/0000-0002-4763-4591 (Hong Zhu)

关键词: 阿尔茨海默病, β淀粉样蛋白, 认知功能障碍, 细胞凋亡, 氧化应激, 神经元损伤, 成纤维细胞生长因子13, 磷脂酰肌醇-3-激酶, AKT, 糖原合成酶激酶3β

Abstract: Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients, and that it plays a vital role in the learning and memory. However, the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear. In this study, we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β (Aβ1–42)-induced into bilateral hippocampus. We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13. The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats. After overexpression of fibroblast growth factor 13, learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved. Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione, superoxide dismutase, phosphatidylinositol-3-kinase, AKT and glycogen synthase kinase 3β, and anti-apoptotic factor BCL. Furthermore, fibroblast growth factor 13 overexpression decreased the number of apoptotic cells, expression of pro-apoptotic factor BAX, cleaved-caspase 3 and amyloid-β expression, and levels of tau phosphorylation, malondialdehyde, reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats. The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3β signaling pathway.

Key words: AKT, Alzheimer’s disease, amyloid-β, apoptosis, cognitive dysfunction, fibroblast growth factor 13, glycogen synthase kinase 3β, neuronal damage, oxidative stress, phosphatidylinositol-3-kinase