电压门控钙离子通道CaV1.2促进小鼠胼胝体而非运动皮质中成年少突胶质祖细胞的存活  

The voltage-gated calcium channel CaV1.2 promotes adult oligodendrocyte progenitor cell survival in the mouse corpus callosum but not motor cortex

作　　者：Pitman KA Ricci R Gasperini R Beasley S Pavez M Charlesworth J Foa L Young KM 杜一星(编译) 

机构地区：[1]Menzies Institute for Medical Research,University of Tasmania,Hobart,Australia [2]School of Medicine,University of Tasmania,Hobart,Australia [3]不详

出　　处：《神经损伤与功能重建》2019年第12期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：在整个生命过程中,少突胶质祖细胞(OPC)增殖并分化为有髓的少突胶质细胞。OPC表达的细胞表面受体和通道,包括电压门控钙通道(VGCC),使它们能够感知并响应神经元活动。CaV1.2是发育过程中OPC表达的主要L型VGCC,它能调控发育过程中OPC的分化。然而,尚不清楚CaV1.2是否对健康成年中枢神经系统(CNS)中的OPC行为有着相似的影响。为了研究CaV1.2在成年期中的作用,我们通过对60 d的Cacna1cfl/fl小鼠(对照组)和Pdgfrα-CreER::Cacna1cfl/fl小鼠(CaV1.2敲除组)给予他莫昔芬,从而实现条件性敲除OPC中的CaV1.2通道。全细胞膜片钳分析显示,CaV1.2敲除使成年OPC中钙离子通过L型电压门控钙通道内流降低了约60%,这证实了它仍然是成年OPC表达的主要L型VGCC。成年OPC中条件性地敲除CaV1.2,可显着提高OPC增殖能力,但不影响新产生的少突胶质细胞的数量,也不影响其形成的节间体的长度或数量。出乎意料的是,CaV1.2敲除导致胼胝体中OPC的大量损失,以至于在他莫昔芬给药后7 d,CaV1.2敲除小鼠的OPC密度仅为对照小鼠的约42%。OPC密度在CaV1.2敲除后的2周内恢复,因为丢失的OPC被CaV1.2敲除后残存的OPC所代替。OPC密度在运动皮质及脊髓中不受影响。因此我们得出结论,钙离子通过CaV1.2进入细胞内对于胼胝体OPC的亚群而言是关键的生存信号,但这并非对于成熟CNS中所有OPC都是至关重要的。Throughout life, oligodendrocyte progenitor cells(OPCs) proliferate and differentiate into myelinating oligodendrocytes. OPCs express cell surface receptors and channels that allow them to detect and respond to neuronal activity, including voltage-gated calcium channel(VGCC)s. The major L-type VGCC expressed by developmental OPCs, CaV1.2, regulates their differentiation. However, it is unclear whether CaV1.2 similarly influences OPC behavior in the healthy adult central nervous system(CNS). To examine the role of CaV1.2 in adulthood, we conditionally deleted this channel from OPCs by administering tamoxifen to P60 Cacna1 cfl/fl(control) and Pdgfrα-CreER:: Cacna1 cfl/fl(CaV1.2-deleted) mice. Whole cell patch clamp analysis revealed that CaV1.2 deletion reduced L-type voltage-gated calcium entry into adult OPCs by ~60%, confirming that it remains the major L-type VGCC expressed by OPCs in adulthood. The conditional deletion of CaV1.2 from adult OPCs significantly increased their proliferation but did not affect the number of new oligodendrocytes produced or influence the length or number of internodes they elaborated. Unexpectedly, CaV1.2 deletion resulted in the dramatic loss of OPCs from the corpus callosum, such that 7 days after tamoxifen administration CaV1.2-deleted mice had an OPC density ~42% that of control mice. OPC density recovered within 2 weeks of CaV1.2 deletion, as the lost OPCs were replaced by surviving CaV1.2-deleted OPCs. As OPC density was not affected in the motor cortex or spinal cord, we conclude that calcium entry through CaV1.2 is a critical survival signal for a subpopulation of callosal OPCs but not for all OPCs in the mature CNS.

关 键 词：电压门控钙离子通道1.2 L型钙离子通道alc亚基基因 神经胶质抗原2 凋亡 钙 胼胝体 运动皮质 少突胶质细胞 增殖 生存 电压门控钙通道 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]