National Drug Clinical Trial Institution, Second Affiliated Hospital, Army Medical University, Chongqing, China.
J Mol Endocrinol. 2021 Apr;66(4):259-272. doi: 10.1530/JME-20-0321.
Earlier, it was shown that reversing the downregulation of neuritin expression in the brain improves central neuropathy in diabetic rats. We investigated the protective mechanism of neuritin in diabetic cognitive dysfunction via astrocytes. Further, the impact of the overexpression of neuritin in the cortex and the hippocampus on diabetic cognitive dysfunction and astrogliosis in type 2 diabetic (db/db) mice was assessed. Antagonists were used to inhibit the JAK2/STAT3 signaling pathway in U-118MG, an astrocyte cell line. Immunofluorescence, Western blotting, and real-time PCR were performed. Neuritin overexpression in the hippocampus of db/db mice significantly ameliorated cognitive dysfunction, hippocampal neuronal impairment, and synaptic plasticity deterioration, and inhibited astrogliosis and the JAK2/STAT3 signaling pathway in the hippocampus. Neuritin suppressed the JAK2/STAT3 signaling pathway to inhibit lipopolysaccharide-induced gliosis in U-118MG cells. It was observed that neuritin regulates the JAK2/STAT3 signaling pathway in astrocytes to inhibit astrogliosis and improve diabetic cognitive dysfunction.
先前的研究表明，逆转脑中神经黏附素表达的下调可以改善糖尿病大鼠的中枢神经病变。我们通过星形胶质细胞研究了神经黏附素在糖尿病认知功能障碍中的保护机制。此外，还评估了在 2 型糖尿病（db/db）小鼠的皮质和海马中过表达神经黏附素对糖尿病认知功能障碍和星形胶质细胞增生的影响。利用拮抗剂抑制星形胶质细胞系 U-118MG 中的 JAK2/STAT3 信号通路。进行免疫荧光、Western blot 和实时 PCR 分析。db/db 小鼠海马中神经黏附素的过表达显著改善了认知功能障碍、海马神经元损伤和突触可塑性恶化，并抑制了海马中的星形胶质细胞增生和 JAK2/STAT3 信号通路。神经黏附素通过抑制 JAK2/STAT3 信号通路抑制脂多糖诱导的 U-118MG 细胞中的神经胶质增生。研究发现，神经黏附素通过调节星形胶质细胞中的 JAK2/STAT3 信号通路抑制星形胶质细胞增生，改善糖尿病认知功能障碍。
