School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
Department of Histology and Embryology, Capital Medical University, Beijing, China.
Neurosci Lett. 2020 Apr 23;725:134872. doi: 10.1016/j.neulet.2020.134872. Epub 2020 Feb 26.
Studies have demonstrated that the failure of oligodendrocyte precursor cells (OPCs) differentiation as a major cause of remyelination failure in demyelinating disease. The reasons for this failure are not completely understood. We hypothesized that the present of myelin debris in CNS play an important role in poor OPCs differentiation in the mouse model of demyelinating disease.
Mice were fed by the food mixed with normal or 0.2 % cuprizone (CPZ) for 6 weeks. Then the learning and memory impairment were tested by Morris water maze test. The spontaneous alternation behavior and depression-like symptoms were assessed by tail suspension test and open filed test. The number of OPCs and oligodendrocytes were counted by immunofluorescence. After exposed to CPZ for 6 weeks, the mice were then receiving stereotactic injection of NEP1-40 into the CA3 of hippocampus. The behavioral, learning and memory changes were assessed by tail suspension test and open field test. The differentiation of OPCs were detected by immunofluorescence and western blot.
The mice in CPZ group are more likely to show signs of depression and they showed impairment of long-term learning and memory function. The differentiation of OPCs were impaired in CPZ group. We found that mice treated with NEP1-40 showed less depression-like symptom in TST and higher locomotor activity in the OFT than the mice treated with PBS.
Our study suggest that NEP1-40 can promote OPC differentiation and survival. Further study should focus on the effect of NEP1-40 on the differentiation and survival of OPCs in vitro.
研究表明，少突胶质前体细胞（OPC）分化失败是脱髓鞘疾病中髓鞘再生失败的主要原因。导致这种失败的原因尚不完全清楚。我们假设中枢神经系统中髓鞘碎片的存在在脱髓鞘疾病的小鼠模型中对 OPC 分化不良起着重要作用。
用正常或 0.2%的 Cuprizone（CPZ）混合饲料喂养小鼠 6 周。然后通过 Morris 水迷宫测试测试学习和记忆障碍。通过悬尾试验和旷场试验评估自发交替行为和抑郁样症状。通过免疫荧光计数 OPC 和少突胶质细胞的数量。暴露于 CPZ 6 周后，将 NEP1-40 立体定向注射到海马 CA3 区。通过悬尾试验和旷场试验评估行为、学习和记忆变化。通过免疫荧光和 Western blot 检测 OPC 的分化。
CPZ 组的小鼠更容易出现抑郁症状，并且表现出长期学习和记忆功能障碍。CPZ 组的 OPC 分化受损。我们发现，用 NEP1-40 处理的小鼠在 TST 中表现出较少的抑郁样症状，在 OFT 中表现出较高的运动活性，而用 PBS 处理的小鼠则没有。
我们的研究表明，NEP1-40 可以促进 OPC 的分化和存活。进一步的研究应集中在 NEP1-40 对体外 OPC 分化和存活的影响上。
