Wang Li-Ping, Geng Jieli, Liu Chang, Wang Yuyang, Zhang Zhijun, Yang Guo-Yuan
Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Front Aging Neurosci. 2022 May 25;14:846739. doi: 10.3389/fnagi.2022.846739. eCollection 2022.
Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice ( = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism . The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group ( < 0.05). The diabetic mice had less exploratory behavior compared to the control ( < 0.05). However, the diabetic mice were more likely to show anxiety ( < 0.05) and depression ( < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment ( < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.
近期临床研究表明，糖尿病患者神经行为障碍的发病率有所上升。研究还发现，糖尿病的严重程度与磁共振成像上白质高信号的进展之间存在关联，这增加了发生认知障碍的风险。由于少突胶质前体细胞参与了缺血性脑损伤后的白质修复和重塑，我们探讨了高血糖诱导的神经行为缺陷是否与少突胶质前体细胞功能障碍有关。成年雄性C57BL/6小鼠（n = 40）被随机分为4周糖尿病组、8周糖尿病组和对照组。通过注射链脲佐菌素诱导实验性糖尿病小鼠。分别通过莫里斯水迷宫、旷场试验、高架十字迷宫和悬尾试验评估学习和认知功能、探索性、焦虑和抑郁行为。进行神经元胶质抗原2和髓鞘碱性蛋白的免疫荧光染色。将少突胶质前体细胞在不同葡萄糖水平下培养以探索可能的机制。与对照组相比，4周和8周糖尿病小鼠的学习和认知功能减弱（P < 0.05）。与对照组相比，糖尿病小鼠的探索性行为较少（P < 0.05）。然而，与对照组相比，糖尿病小鼠更易出现焦虑（P < 0.05）和抑郁（P < 0.01）。进一步研究表明，糖尿病小鼠少突胶质前体细胞数量和髓鞘碱性蛋白表达水平降低，在高血糖环境中迁移和存活能力受到抑制（P < 0.05）。我们的结果表明，糖尿病诱导的神经功能缺损与少突胶质前体细胞数量减少和功能障碍有关。
