Selective glutamate receptor antagonists can induce or prevent axonal sprouting in rat hippocampal slice cultures
Selective glutamate receptor antagonists can induce or prevent axonal sprouting in rat hippocampal slice cultures
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DOI：
10.1073/pnas.96.20.11631
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Thompson, SM
中科院分区：
文献类型：
--
作者：
McKinney, RA;Lüthi, A;Thompson, SM
在海马切片培养物中切断Schaffer侧支通路后，在CA 3区诱导反应性发芽，并最终恢复CA 1和CA 3区之间的突触传递。利用这个模型，我们研究了离子型谷氨酸受体在轴突发芽和功能性突触再生中的作用。我们发现，既没有反应性发芽，也没有突触传递的功能恢复发生在非N-甲基-D-天冬氨酸（NMDA）受体拮抗剂6-硝基-7-氨磺酰苯并喹喔啉-2，3-二酮（CNQX）的存在下。相反，NMDA受体拮抗剂甲基-10，11-二氢-5-H-二苯并环庚烯-5，10-亚胺（MK-801）或3-（RS）-2-羧基哌嗪-4-基）-丙基-1-膦酸（CPP）不干扰这些过程。此外，我们观察到应用NMDA受体拮抗剂可诱导未损伤培养物中大量轴突发芽和微型兴奋性突触后电流频率增加。因此，我们的研究结果表明，NMDA和非NMDA受体在海马损伤后的反应性发芽和突触传递的恢复中发挥不同的作用。非NMDA受体的激活似乎是这些过程发生所必需的，而NMDA受体的激活抑制生长相关蛋白-43的表达和轴突生长。
After the transection of the Schaffer collateral pathway in hippocampal slice cultures, reactive sprouting is induced in the CA3 area, and eventually synaptic transmission between areas CA1 and CA3 is restored. Using this model, we have studied the role of ionotropic glutamate receptors in the initiation of axonal sprouting and the regeneration of functional synapses. We show that neither reactive sprouting nor functional recovery of synaptic transmission occur in the presence of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-nitro-7-sulfamoylbenzoquinoxaline-2,3-dione (CNQX). In contrast, the NMDA receptor antagonists methyl-10,11-dihydro-5-H-dibenzocyclohepten-5,10-imine (MK-801) or 3-(RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) did not interfere with these processes. Moreover, we observed that the application of NMDA receptor antagonists induced massive axonal sprouting and an increase in the frequency of miniature excitatory postsynaptic currents in unlesioned cultures. Our results thus indicate that NMDA and non-NMDA receptors exert a differential effect on reactive sprouting and the recovery of synaptic transmission after injury in the hippocampus. Activation of non-NMDA receptors appears necessary for these processes to occur, whereas activation of NMDA receptors suppresses growth-associated protein -43 expression and axonal outgrowth.