Department of General Practice, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Department of Emergency Medicine, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Mediators Inflamm. 2019 Jul 16;2019:4315038. doi: 10.1155/2019/4315038. eCollection 2019.
Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.
糖尿病（DM）患者表现出焦虑风险增加。高水平的焦虑也被证明会增加糖尿病患者的压力，这可能导致不良的临床结局。糖尿病患者焦虑障碍发展的机制尚不清楚。因此，目前尚无可用的治疗方法。在这里，我们检验了这样一个假设，即 DM 小鼠海马区的神经胶质细胞可能是导致其焦虑样行为的原因。此外，我们假设使用抗抑郁药氟西汀治疗可以减轻焦虑行为并防止 DM 小鼠的神经胶质细胞（少突胶质细胞和星形胶质细胞）失调。糖尿病小鼠接受链脲佐菌素（STZ）单次注射，然后用氟西汀治疗。然后，用 Y 迷宫、旷场、明暗过渡和高架十字迷宫测试来测量焦虑和认知状态。完成这些行为测试后，处死小鼠，用 Western blot 检测海马组织中的少突胶质细胞和星形胶质细胞标志物蛋白。重点关注成熟的少突胶质前体细胞（OPC）及其标志物蛋白，以测量其增殖和分化。我们发现氟西汀可以有效减轻糖尿病小鼠的焦虑水平并改善其认知功能障碍。同时，氟西汀抑制了 STZ 暴露小鼠的星形胶质细胞激活，防止了髓鞘碱性蛋白（MBP）的丢失，并影响了这些糖尿病小鼠中 OPCs 的功能。结果表明，糖尿病小鼠大脑中这些神经胶质细胞的变化可能与 DM 小鼠的高焦虑水平和认知缺陷有关。氟西汀可以通过抑制星形胶质细胞激活和修复少突胶质细胞损伤来改善高焦虑水平并预防认知缺陷。
