脑脊液中D-Ser对齿状回颗粒细胞层突触传递和可塑性相关蛋白的作用研究  

Effects of D-serine in CSF on LTP in dentate gyrus granule cell synapses and neuroplasticity-associated proteins in vivo

作　　者：谢奇辰[1,2] 殷卫东[1,3] 钱天秀 陈思维[1,2] 王晓英 

机构地区：[1]中国医学科学院药用植物研究所药理中心,北京100193 [2]沈阳药科大学生命科学与生物制药学院,辽宁沈阳110016 [3]山东淄博临淄区人民医院,山东淄博255400

出　　处：《中国药理学通报》2012年第5期651-655,共5页Chinese Pharmacological Bulletin

基　　金：高等学校博士学科点专项科研基金(No 200800231108);中央级公益性科研院所基本科研业务费(No 2008QN39);人事部留学回国人员择优资助项目

摘　　要：目的研究了脑脊液中D-丝氨酸(D-Ser)对齿状回颗粒细胞层突触传递和突触可塑性相关蛋白的作用。方法利用手术种植给药瘘管方法,在手术后第3天开始,隔天予以对照IgG和抗D-Ser IgG,给药3 d。之后采用胞外记录方法,刺激电极置于海马穿通纤维,记录齿状回颗粒细胞层LTP的诱导的变化,采用分子生物学方法检测皮层和海马突触可塑性相关蛋白表达的变化。结果抗D-Ser IgG连续中枢注射后,齿状回颗粒细胞层群峰电位的幅度明显下降,LTP的诱导受到明显阻断,同时海马和皮层部位突触可塑性相关蛋白的表达也发生了明显的变化。GAP-43在皮层和海马的表达分别升高约52%,58%。而MAP2的表达皮层降低约32%,海马降低约59%。皮层synapsinⅠ表达降低约45%,海马synapsinⅠ降低约57%。结论海马部位突触可塑性相关蛋白的表达对脑脊液中D-Ser浓度的变化表现出更高的敏感性,脑脊液中D-Ser具有重要的中枢调节作用,为神经精神相关疾病患者的临床治疗新药物和新方法的发现提供了理论支持。Aim To investigate the effects of D-serine in CSF on LTP in perforant path-dentate gyrus granule cell synapses and synaptic plasticity-associated proteins.Methods Cannula was implanted at the lateral ventricle.Both control rabbit IgG and anti-D-serine IgG were injected 3 times every other day from the third day after surgery.And then extracellular recording technique was used to record the population spike in paforant path-dentate gyrus granule cell synapses in vivo.Cortex and hippocampus were collected to detect the expression of the synaptic plasticity related protein with the use of molecular biology technique.Results Anti-D-serine IgG significantly impaired LTP induction in dentate gyrus granule cell synapses and GAP43 expression was both increased in cortex and hippocampus by 52% and 58%,and no difference was found between two regions.Whereas rats treated with Anti-Dserine IgG showed MAP-2 expression was decreased by 32% and 59% and synapsin I by 45 % and 57% in cortex and hippocampus respectively.Conclusion The synaptic plasticity associated protein in hippocampus shows more sensitivity to D-Ser concentration alteration.D-serine in CSF has regulatory effects and provides an insight into schizophrenic and AD treatment and new drug development.

关 键 词：脑脊液 突触可塑性 LTP D-丝氨酸 生长相关蛋白 海马 

分 类 号：R742.1[医药卫生—神经病学与精神病学]