Implication of NMDA type glutamate receptors in neural regeneration and neoformation of synapses after excitotoxic injury in the guinea pig cochlea
Implication of NMDA type glutamate receptors in neural regeneration and neoformation of synapses after excitotoxic injury in the guinea pig cochlea
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DOI：
10.1016/s0736-5748(96)00116-5
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发表时间：
1997-07-01
影响因子：
1.8
通讯作者：
Puel, JL
中科院分区：
文献类型：
--
作者：
dAldin, CG;Ruel, J;Puel, JL
在成年哺乳动物的耳蜗中，神经纤维的再生能力已经被观察到，在通过各种方式破坏Corti器官或横断内耳道的耳蜗神经后。基于谷氨酸作为神经递质在哺乳动物耳蜗感觉毛细胞和听神经末梢树突之间的突触中的作用，我们在之前的研究中建立了局部应用谷氨酸激动剂α -氨基-3-羟基-5-甲基异恶唑丙酸（AMPA）破坏传入神经末梢后神经再生和突触形成的体内模型。在再神经支配过程中进行的原位杂交实验显示，螺旋神经节神经元中n -甲基- d -天冬氨酸（NMDA）受体NR1亚基的mRNA编码过表达，表明这些受体与神经再生过程有关。本研究旨在研究NMDA受体在豚鼠耳蜗听觉树突再生和突触修复中的功能意义，通过在正常功能恢复期间阻断NMDA受体。在第一组实验中，我们记录了累积剂量（0.03-10 mM） NMDA拮抗剂DL 2-氨基-5-磷酸戊酸（D-AP5）急性淋巴周围灌注后的复合动作电位，以确定药物的效率。在第二组实验中，局部应用谷氨酸激动剂AMPA破坏听觉树突。通过渗透微泵应用拮抗剂D-AP5阻断NMDA，可延缓听觉树突功能恢复和再生。我们的研究结果支持了一种假设，即除了作为一种快速递质外，谷氨酸还通过激活NMDA受体而具有神经营养作用。(c) 1997 isdn。
In the adult mammalian cochlea, the ability of nerve fibres to regenerate has been observed following disruption of the organ of Corti by various means, or transsection of the cochlear nerve in the internal auditory meatus. Based upon the implication of glutamate as a neurotransmitter al synapses between sensory hair cells and terminal dendrites of the auditory nerve in the mammalian cochlea, we have developed, in a previous study, an in vivo model of neural regeneration and formation of synapses after the destruction of the afferent nerve endings by local application of the glutamate agonist alpha-amino-3-hydroxy-5-methyl-isoxazol-propionic acid (AMPA). In situ hybridization experiments performed during the re-innervation process revealed an overexpression of mRNA coding for NR1 subunit of N-methyl-D-aspartate (NMDA) receptors in the spiral ganglion neurons, suggesting that these receptors are implicated in neural regenerative processes. The present study has been designed to study the functional implication of NMDA receptors in the regrowth and synaptic repair of auditory dendrites in the guinea pig cochlea, by blocking the NMDA receptors during the period of normal functional recovery. In a first set of experiments, we recorded compound action potential after acute perilymphatic perfusion of cumulative doses (0.03-10 mM) of DL 2-amino-5-phosphonovalerate (D-AP5), a NMDA antagonist, to determine the efficiency of the drug. In a second set of experiments, the auditory dendrites were destroyed by local application of the glutamate agonist AMPA. The blockage of NMDA by the antagonist D-AP5 applied with an osmotic micropump delayed the functional recovery and the regrowth of auditory dendrites. The findings of our study support the hypothesis that, in addition to acting as a fast transmitter, glutamate has a neurotrophic role via the activation of NMDA receptors. (C) 1997 ISDN.