贝沙罗汀拮抗Aβ_(25-35)诱导的海马CA1区锥体神经元谷氨酸能突触传递的抑制效应

Antagonistic effect of bexarotene on Aβ_(25-35)-induced inhibiting action in glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons

目的:初步探讨β淀粉样蛋白Aβ_(25-35)损伤海马CA1区兴奋性突触的靶点及贝沙罗汀的可能拮抗效应。方法:以出生7~14 d Wistar大鼠海马脑片为研究对象,采用全细胞膜片钳技术,在电压钳模式下记录大鼠海马脑片CA1区锥体细胞自发兴奋性突触后电流(s EPSCs)和微小兴奋性突触后电流(mEPSCs),分析不同组神经元s EPSCs和mEPSCs幅度及频率的差异。结果:与对照组相比,经Aβ_(25-35)(1μmol/L)处理后,海马神经元sEPSCs与mEPSCs平均幅度和平均频率都显著降低(均P<0.05)。向Aβ_(25-35)处理过的海马脑片中加入贝沙罗汀(5μmol/L)后,sEPSCs与mEPSCs平均幅度和平均频率较Aβ_(25-35)组都显著提高(均P<0.05)。贝沙罗汀处理组sEPSCs与mEPSCs平均频率和平均幅度与对照组水平无显著性差异(均P>0.05)。结论:Aβ_(25-35)可作用于CA1区,导致海马锥体神经元兴奋性突触后电位降低,突触功能损伤,贝沙罗汀通过作用于突触前和突触后位点拮抗Aβ_(25-35)的损伤效应。

Objective： To explore the damage effect target of Aβ25-35on hippocampal CA1 excitatory synapses and the possible antagonistic effect of bexarotene. Methods： Postnatal 7-14-day-old Wistar rats were used as the research subjects. Using a whole-cell patch clamp technique, and in voltage-clamp mode, we recorded spontaneous excitatory postsynaptic currents （sEPSCs） and miniature excitatory postsynaptic currents （mEPSCs） of CA1 pyramidal neurons in hippocampal slices. The changes of the amplitude and frequency of the sEPSCS and mEPSCs in each group were analyzed. Results： After Aβ25–35 （1 umol/L） application, the average amplitude and frequency of sEPSCs and mEPSCs were significantly reduced compared with the control group （P〈 0.05）. Following application of bexarotene （5 umol/L） to Aβ25-35 group, the average amplitude and frequency of sEPSCs and mEPSCs were significantly increased compared with the Aβ25–35 group（P〈 0.05）; and compared with the control group, the difference was not statistically significant （P〉 0.05）. Conclusion： Aβ25-35 has a damage effect on CA1 pyramidal neurons, resulting in the decrease of excitatory postsynaptic potential and synaptic function damage, while bexarotene has a presynaptic and postsynaptic site of action to antagonize Aβ25-35-induced synaptic dysfunction in hippocampal CA1 pyramidal neurons.