髓鞘形成相关NMDA-R亚基在精神分裂症小鼠模型中的变化

Alterations of myelination-related NMDA-R subunits in schizophrenia mouse model

目的:探讨髓鞘形成相关N-甲基-D-天冬氨酸受体(NMDA-R)亚基在MK-801诱导的精神分裂症小鼠模型大脑中的变化。方法:35只雄性C57BL/6J小鼠,随机分为:对照组(control)和地卓西平马来酸盐处理组(MK-801),利用旷场实验、探孔实验及高架十字迷宫检测小鼠行为学改变,免疫荧光染色观察小鼠大脑NMDAR亚基NR1的表达,real time RT-PCR检测髓鞘形成相关NMDA-R亚基NR1、NR2C和NR3A mRNA的表达。结果:与对照组小鼠相比,MK-801处理组在旷场内10 min总运动路程较对照组显著增加;3 min及5 min内探孔次数较对照组显著降低;模型组小鼠在开臂内停留总时间较对照组显著降低。NR1在小鼠神经细胞胞膜、轴突周围和髓鞘部位均有表达。大脑皮层、海马内的NMDA-R亚基NR1,NR2C及NR3A mRNA的表达在两组间均无显著差异;胼胝体区域NR1和NR2C mRNA表达在两组间同样无显著差异;但相较于对照组,MK-801慢性给药组小鼠胼胝体区域NMDA-R亚基NR3A mRNA表达显著上调。结论:NMDA-R在少突胶质细胞、髓鞘等部位确有表达;胼胝体部位NR3A亚基上调可能在MK-801诱导的精神分裂症中发挥作用。

Objective:To investigate the expression changes of different subunits of N-methyl-D-aspartate receptor(NMDA-R)in the brain of mice with schizophrenia-like behavior induced by MK-801.Methods:Thirty-five male C57 BL/6 mice(10 weeks old)were randomly divided into dizocilpine(MK-801)chronic administration group(for 2 weeks)and control group(normal saline).The behavioral changes of mice were tested with open field test,hole-board test and elevated plus maze.The location of NMDA-R was detected with immunofluorescence,and the mRNA expression of NMDA-R NR1,NR2 C,and NR3 A was detected with real time RT-PCR.Results:MK-801 treated mice showed increased spontaneous activity,decreased exploration of new environments,and significantly increased anxiety.NR1 is expressed on neurons,around axons and myelin sheath.The expression of NMDA-R subunits NR1,NR2 C,and NR3 A mRNA in cerebral cortex and hippocampus showed no significant difference between the two groups.The expression of NR1 and NR2 C mRNA in the corpus callosum was also not significantly different between the two groups.However,compared with the control group,the NMDA-R subunit NR3 A mRNA expression was significantly up-regulated in the corpus callosum of the MK-801 chronic administration group.Conclusion:The upregulation of NR3 A subunit in corpus callosum may play a role in schizophenic mice model induced by MK-801.