APP/PS1转基因小鼠海马内少突胶质细胞变化的体视学研究

目的:定量研究APP/PS1转基因小鼠海马内少突胶质细胞(OLG)的改变,探讨β-淀粉样蛋白(Aβ)对OLG的影响。方法:随机选取10月龄雄性APP/PS1转基因小鼠(AD组)和10月龄同窝生雄性野生型小鼠(WT组)各13只,运用Morris水迷宫检测各组小鼠的空间学习和记忆能力;运用体视学方法计数各组小鼠海马CA1、CA2-3和齿状回(DG)内Olig2+细胞和2',3'-环核苷酸3'-磷酸二酯酶(CNPase)阳性细胞总数;体外培养小鼠少突胶质前体细胞(MOPC),给予Aβ1-42,运用real time RT-PCR和Western Blot检测OLG相关蛋白的表达水平和含量。结果:AD小鼠逃避潜伏期显著性长于WT小鼠(P<0.05),穿台次数显著性少于WT小鼠(P<0.05);AD小鼠海马各区Olig2+细胞总数均较WT小鼠显著性增加(P<0.05),且与逃避潜伏期呈正相关,与穿台次数呈负相关,而各区CNPase+细胞总数均较WT小鼠显著性减少(P<0.05),且与逃避潜伏期呈负相关;Aβ1-42干预后MOPC的NG2及CNPase的mRNA水平显著性降低(P<0.05),Olig2含量也显著性降低(P<0.05)。结论:APP/PS1转基因小鼠海马内存在成熟OLG丢失、少突胶质细胞系异常增殖;Aβ可能引起OLG损伤和发育异常;保护海马成熟OLG以及调控OLG发育可能是防治AD的有效策略。

The changes of oligodendrocytes in the hippocampus of APP/PS1 transgenic mice: A stereological study

Objective:To quantitatively study the changes of oligodendrocytes(OLG)in the hippocampus of APP/PS1 transgenic mice,and investigate the effects of amyloid-beta(Aβ)on the OLG in vitro.Methods:Thirteen 10-month-old male APP/PS1 transgenic mice(AD group)and Thirteen 10-month-old male wild-type littermates(WT group)were randomly selected.The spatial learning and memory abilities of each group mice were tested with Morris water maze.The total numbers of Olig2+cells and 2',3'-cyclic nucleotide 3'-phosphodiesterase+(CNPase+)cells in the CA1 field,CA2-3 field and dentate gyrus(DG)of the hippocampus of each group mice were investigated using stereological method.Mouse oligodendrocyte precursor cells(MOPC)were cultured in vitro and given exogenous Aβ1-42.The expression level and content of OLG related proteins were detected with real time RT-PCR and Western Blot.Results:The escape latency of AD mice was significantly longer than WT mice(P<0.05),and Platform-crossing frequency of AD mice was significantly less than WT mice(P<0.05).The total numbers of Olig2+cells in the hippocampus of AD mice were all significantly increased compared with WT mice(P<0.05),positively correlated with the escape latency and negatively correlated with Platform-crossing frequency.The total numbers of CNPase+cells in the hippocampus of AD mice were significantly decreased compared with WT mice(P<0.05),negatively correlated with the escape latency.After exogenous Aβ1-42 was given,the mRNA levels of NG2 and CNPase in the MOPC were decreased(P<0.05)and the protein level of Olig2 was significantly decreased(P<0.05).Conclusion:The loss of mature OLG and abnormal proliferation of oligodendrocytes lineage cell in the hippocampus of APP/PS1 transgenic mice.Aβcould cause the damage and abnormal development of OLG.Protecting the mature OLG and regulating the development of OLG in the hippocampus may be an effective strategy for the prevention and treatment of AD.