Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
Neurochem Int. 2023 Oct;169:105591. doi: 10.1016/j.neuint.2023.105591. Epub 2023 Aug 4.
Diabetic cognitive impairment (DCI) is a complex complication of diabetes in the central nervous system, and its pathological mechanism is still being explored. Astrocytes are abundant glial cells in central nervous system that perform diverse functions in health and disease. Accumulating excellent research has identified astrocyte dysfunction in many neurodegenerative diseases (such as Alzheimer's disease, aging and Parkinson's disease), and summarized and discussed its pathological mechanisms and potential therapeutic value. However, the contribution of astrocytes to DCI has been largely overlooked. In this review, we first systematically summarized the effects and mechanisms of diabetes on brain astrocytes, and found that the diabetic environment (such as hyperglycemia, advanced glycation end products and cerebral insulin resistance) mediated brain reactive astrogliosis, which was specifically reflected in the changes of cell morphology and the remodeling of signature molecules. Secondly, we emphasized the contribution and potential targets of reactive astrogliosis to DCI, and found that reactive astrogliosis-induced increased blood-brain barrier permeability, glymphatic system dysfunction, neuroinflammation, abnormal cell communication and cholesterol metabolism dysregulation worsened cognitive function. In addition, we summarized effective strategies for treating DCI by targeting astrocytes. Finally, we discuss the application of new techniques in astrocytes, including single-cell transcriptome, in situ sequencing, and prospected new functions, new subsets and new targets of astrocytes in DCI.
糖尿病性认知功能障碍（DCI）是糖尿病在中枢神经系统的一种复杂并发症，其病理机制仍在探索中。星形胶质细胞是中枢神经系统中丰富的神经胶质细胞，在健康和疾病中发挥着多种功能。大量优秀的研究已经确定星形胶质细胞功能障碍存在于许多神经退行性疾病（如阿尔茨海默病、衰老和帕金森病）中，并对其病理机制和潜在治疗价值进行了总结和讨论。然而，星形胶质细胞对 DCI 的贡献在很大程度上被忽视了。在这篇综述中，我们首先系统地总结了糖尿病对大脑星形胶质细胞的影响和作用机制，发现糖尿病环境（如高血糖、晚期糖基化终产物和脑胰岛素抵抗）介导了大脑反应性星形胶质细胞增生，具体表现在细胞形态的变化和特征分子的重塑上。其次，我们强调了反应性星形胶质细胞增生对 DCI 的贡献和潜在靶点，发现反应性星形胶质细胞增生诱导的血脑屏障通透性增加、神经淋巴系统功能障碍、神经炎症、异常细胞通讯和胆固醇代谢失调会使认知功能恶化。此外，我们还总结了通过针对星形胶质细胞治疗 DCI 的有效策略。最后，我们讨论了新技术在星形胶质细胞中的应用，包括单细胞转录组、原位测序，并展望了星形胶质细胞在 DCI 中的新功能、新亚群和新靶点。
