NMDA受体功能降低而非增强参与皮质酮诱发的海马长时程增强减弱  

Hypofunction rather than hyperfunction of NMDA receptor plays an important role in long-term potentiation deficit by corticosterone

作　　者：于琪 黄晏 周文霞 YU Qi;HUANG Yan;ZHOU Wen-xia(School of Pharmaceutical Sciences,Yantai University,Yantai 264005,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]烟台大学药学院,山东烟台264005 [2]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2021年第6期412-419,共8页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的研究皮质酮(CORT)致长时程增强(LTP)减弱时,N-甲基-D-天冬氨酸(NMDA)受体功能的变化。方法取C57BL/6J小鼠的海马制备300μm的脑片,分别采用含不同药物的人工脑脊液循环灌流75 min;以0.033 Hz单脉冲刺激诱发场兴奋性突触后电位(fEPSP),以单次高频刺激(HFS,100 Hz,100串)为LTP诱发刺激;选择背侧海马脑片Schaffer-CA1通路记录fEPSP斜率的变化,反映不同药物或药物组合对海马脑片LTP的影响。结果在0.033 Hz单脉冲刺激下,CORT 1μmol·L^(-1)组fEPSP斜率无明显变化;HFS刺激后,CORT 1μmol·L^(-1)组fEPSP斜率增幅较正常对照组显著减少(P<0.01)。与正常对照组相比,NMDA受体亚型非选择性拮抗剂D-AP510μmol·L^(-1)对fEPSP增幅无显著影响,25和100μmol·L^(-1)显著减小fEPSP增幅(P<0.01);NMDA受体亚型GluN2A选择性拮抗剂TCN-2011μmol·L^(-1)对fEPSP增幅无显著影响,而3和6μmol·L^(-1)显著减小fEPSP增幅(P<0.01);GluN2B选择性拮抗剂Ro25-69810.25μmol·L^(-1)对fEPSP增幅无显著影响,0.5和1.0μmol·L^(-1)显著减小fEPSP增幅(P<0.01)。与CORT组相比,CORT+D-AP510μmol·L^(-1)组、CORT+TCN-2011μmol·L^(-1)组和CORT+Ro25-69810.25μmol·L^(-1)组fEPSP增幅均无显著变化,CORT+D-丝氨酸(NMDA受体共激活剂)10μmol·L^(-1)组fEPSP增幅显著增加(P<0.01)。结论NMDA受体功能降低而非增强是CORT诱发海马LTP减弱的主要原因之一。OBJECTIVE To observe the change of N-methyl-D-aspartate(NMDA)receptor function in a long-term potentiation(LTP)impairment model induced by corticosterone(CORT).METHODS The hippocampus of C57 BL/6 J mice was taken to prepare 300μm-thick brain slices that were treated with artificial cerebrospinal fluid containing different drugs by circulated perfusion of 75 min.A single pulse stimulation of 0.033 Hz was used to elicit field excitatory postsynaptic potential(fEPSP),and LTP was initiated by single high-frequency stimulation(HFS,100 Hz,100 trains)pulses.The Schaffer-CA1 pathway of the dorsal hippocampal slice was chosen to record the change of the fEPSP slope to reflect the effect of different drugs or drug combinations on the hippocampal slice LTP.RESULTS Under0.033 Hz single pulse stimulation,the fEPSP slope of the CORT 1μmol·L^(-1) group did not change significantly.After HFS stimulation,the increase of the f EPSP slope in the CORT 1μmol·L^(-1) group was significantly lower than in the normal control group(P<0.01),suggesting that CORT significantly attenuated LTP without affecting basic synaptic transmission.Compared with the normal control group,the NMDA receptor antagonist D-AP510μmol·L^(-1) had no significant effect on the increase of fEPSP,while 25 and100μmol·L^(-1) significantly reduced the increase of fEPSP(P<0.01).GluN2 A selective antagonist TCN-2011μmol·L^(-1) had no significant effect on the increase of fEPSP,while 3 and 6μmol·L^(-1) significantly curbed the increase of fEPSP(P<0.01).GluN2 B selective antagonist Ro25-69810.25μmol·L^(-1) had no significant effect on the increase of fEPSP,while 0.5 and 1μmol·L^(-1) significantly inhibited the increase of fEPSP(P<0.01).Compared with the CORT group,the CORT+D-AP5(10μmol·L^(-1)),the CORT+TCN-201(1μmol·L^(-1))and the CORT+Ro25-6981(0.25μmol·L^(-1))groups had no significant improvement in terms of fEPSP while the NMDA receptor co-activator D-serine(CORT+D-serine,10μmol·L^(-1))significantly stepped up the increase of fEPSP(P<0.01).CONCL

关 键 词：N-甲基-D-天冬氨酸受体 GluN2A GluN2B 皮质酮 长时程增强 

分 类 号：R966[医药卫生—药理学]