Ikegaya Y, Ikeda Y, Saito H, Nishiyama N
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Biol Pharm Bull. 1998 Mar;21(3):231-4. doi: 10.1248/bpb.21.231.
Using an organotypic slice culture of the hippocampus, the effects of epileptic activities on synapse reorganization following axotomy were investigated. The maximal amplitude of field excitatory postsynaptic potentials that reflected the number of functional synaptic contacts were recorded 7 d after the mossy fibers or Schaffer collaterals were transected at 8 d in vitro. Fifty microM picrotoxin elicited epileptiform bursts, whose severity in the CA1 region was lower than that in the CA3 region. Synapse reformation of the mossy fibers was significantly prevented by picrotoxin, and that of Schaffer collaterals also tended to be attenuated. Ten microM bicuculline, 1 mM pentylenetetrazol or 2 mM 4-aminopyridine also induced epileptic activities in the CA3 region and significantly depressed synapse formation of the mossy fibers. Using cultures of dispersed neurons, we found that the prolonged depolarization of membrane potentials promoted neurite outgrowth. Taken together, we concluded that the preventing effects of epileptic activities on synapse reorganization following axotomy was due to the inhibition of the synaptogenesis process, not to a blockade of axon outgrowth.
利用海马体的器官型切片培养，研究了癫痫活动对轴突切断后突触重组的影响。在体外培养8天时切断苔藓纤维或Schaffer侧支，7天后记录反映功能性突触接触数量的场兴奋性突触后电位的最大幅度。50微摩尔匹鲁卡品引发癫痫样爆发，其在CA1区的严重程度低于CA3区。匹鲁卡品显著抑制了苔藓纤维的突触重塑，Schaffer侧支的突触重塑也有减弱趋势。10微摩尔荷包牡丹碱、1毫摩尔戊四氮或2毫摩尔4-氨基吡啶也在CA3区诱导癫痫活动，并显著抑制苔藓纤维的突触形成。利用分散神经元培养，我们发现膜电位的长时间去极化促进了神经突生长。综上所述，我们得出结论，癫痫活动对轴突切断后突触重组的抑制作用是由于对突触发生过程的抑制，而非轴突生长的阻断。
