Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.
Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou, 121001, Liaoning, China.
J Mol Histol. 2024 Oct;55(5):851-861. doi: 10.1007/s10735-024-10236-y. Epub 2024 Aug 29.
Diabetic cognitive dysfunction (DCD) is a complication of diabetes that seriously affects quality of life. Glucocorticoid-induced transcript 1 (GLCCI1) has been found to be involved in inflammation, apoptosis and autophagy in various diseases. However, the distribution of GLCCI1 in the brain and its role in DCD have not yet been revealed. In addition, the potential therapeutics effects of salidroside (SAL), a phenyl propyl glycoside compound known for its neuroprotective effects in treating DCD are unknow. In the present study, we found that GLCCI1 was localized in hippocampal neurons. C57BL/6 J mice with DCD presented downregulation of GLCCI1 and Bcl-2 and upregulation of p-STAT3/STAT3, Bax, Cleaved Caspase-3/Caspase-3. Overexpression of GLCCI1 or SAL administration relieved DCD, reversed the changes in the expression of these cytokines, and alleviated morphological alterations in hippocampal neurons. Interestingly, SAL alleviated DCD and attenuated the expression of GLCCI1 and p-STAT3, showing similar effects as GLCCI1 overexpression. These findings suggest that the GLCCI1/STAT3 axis plays a crucial role in DCD and is involved in SAL-mediated attenuation of DCD.
糖尿病认知功能障碍（DCD）是糖尿病的一种并发症，严重影响生活质量。糖皮质激素诱导转录物 1（GLCCI1）已被发现参与各种疾病的炎症、细胞凋亡和自噬。然而，GLCCI1 在大脑中的分布及其在 DCD 中的作用尚未被揭示。此外，Salidroside（SAL）作为一种苯丙基糖苷化合物，已知对 DCD 具有神经保护作用，但其潜在的治疗效果尚不清楚。在本研究中，我们发现 GLCCI1 定位于海马神经元。DCD 模型 C57BL/6J 小鼠的 GLCCI1 和 Bcl-2 下调，p-STAT3/STAT3、Bax、Cleaved Caspase-3/Caspase-3 上调。GLCCI1 的过表达或 SAL 给药缓解了 DCD，逆转了这些细胞因子表达的变化，并减轻了海马神经元的形态改变。有趣的是，SAL 缓解了 DCD 并减弱了 GLCCI1 和 p-STAT3 的表达，表现出与 GLCCI1 过表达相似的效果。这些发现表明，GLCCI1/STAT3 轴在 DCD 中起关键作用，并参与了 SAL 介导的 DCD 衰减。
