ATP在海马CA1区长时程增强中的作用及机制

ROLE OF ATP IN LONG-TERM POTENTIATION IN SPINAL DORSAL HORN AND HIPPOCAMPAL CA1 REGION AND ITS UNDERLYING MECHANISM

目的探讨三磷酸腺苷(adenosine5'-triphosphate,ATP)在海马CA1区长时程增强(LTP)中的作用及机制。方法本研究采用海马在体电生理记录和免疫组织化学方法。在体电生理记录海马CA1区兴奋性突触后电位(field excitatory postsynaptic potentials,fEPSPs)以及高频刺激诱导的LTP,免疫组织化学观察海马CA1区小胶质细胞的激活情况。结果①侧脑室内给予ATP不影响基础性fEPSPs,但能显著抑制高频刺激诱导的LTP,高频刺激后fEPSPs平均幅度较生理盐水对照组明显降低。②侧脑室内给予P2X7受体拮抗剂oxidized ATP,可阻止ATP对海马CA1区LTP的抑制。③给予ATP后30 min,海马CA1区的小胶质细胞明显被激活;侧脑室内给予小胶质细胞抑制剂美满霉素或TNF-α中和抗体,均可阻止ATP对海马CA1区LTP的抑制。结论 ATP可能与P2X7受体结合,激活小胶质细胞抑制海马CA1区LTP,TNF-α参与此作用。

Objective To explore the role of ATP in long - term potentiation （LTP） in hippocampl CA1 re- gion and its underlying mechanism. Methods Electrophysiological recording in hippocampus in vivo and immunohistochemistry were used in the study. The field excitatory postsynaptic potentials （fEPSPs） and high -frequency stimuli （HFS） - induced LTP were recorded in hippocampal CA1 region, and the activation of mieroglia in hippocampal CA1 region was examined using immunohistochemistry technique. Results （1）Intracerebroventricular （ i. e. v. ） injection of ATP did not affect the baseline synaptic transmission, but significantly suppressed the HFS -induced LTP, with decreased average amplitude of fEPSPs in ATP group, compared to that in the control （NS） group. （2）i. c.v. injection of the P2X7 antagonist oxidized ATP prevented ATP - mediated LTP inhibition. （3）At 30 min after i. c. v. injection of ATP, mieroglia in hippocampal CA1 region were significantly activated; i. c. v. injection of microglia inhibitor （mino- cycline） or TNF - α neutralization antibody reversed the ATP inhibition of LTP induction. Conclusion ATP might activate microglia and inhibit hippoeampal CA1 LTP by binding to P2X7 receptors and TNF - α might be involved in the process.