Lerner-Natoli M, Ladrech S, Renard N, Puel J L, Eybalin M, Pujol R
INSERM U254 and Université de Montpellier I, CHU Hôpital St Charles, France.
Brain Res. 1997 Feb 21;749(1):109-19. doi: 10.1016/s0006-8993(96)01306-6.
A suitable model of sudden deafness occurring after acoustic trauma or ischemia, is obtained in guinea pigs by an acute intracochlear perfusion of 200 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate analog. By overloading the AMPA/kainate receptors, located post-synaptically to inner hair cells (IHCs), it induces a massive swelling of primary auditory neuron dendrites, which disconnects the IHCs. This synaptic uncoupling and the resulting hearing loss are followed by a progressive regrowth of dendrites, which make new synapses with IHCs, leading to a functional recovery of auditory responses that is completed after 5 days. Knowing the role of protein kinase C in neuroplastic events, we studied the expression of its isoforms alpha,beta(I,II) and gamma, respectively pre- and post-synaptic, in auditory neurons at various times after AMPA administration. In untreated cochleas, we observed an expression of PKC alpha,beta(I,II) and gamma in cell bodies of primary auditory neurons. After the intracochlear administration of AMPA, both isozymes were transiently overexpressed, with a peak at 3-6 h, followed by a decrease after about 24 h. At this point in time immuno-electron microscopy revealed some regrowing dendrites immunoreactive for PKCgamma. Five days after AMPA, when the auditory responses were restored, PKCgamma levels were still elevated in ganglion cell bodies.
通过向豚鼠耳蜗内急性灌注200微摩尔的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA，一种谷氨酸类似物），可获得一种适用于模拟声创伤或缺血后突发耳聋的模型。通过使位于内毛细胞（IHC）突触后位置的AMPA/海人藻酸受体过载，它会诱导初级听觉神经元树突大量肿胀，从而使内毛细胞失去连接。这种突触解偶联以及由此导致的听力损失之后，树突会逐渐再生，并与内毛细胞形成新的突触，从而导致听觉反应功能恢复，该恢复过程在5天后完成。鉴于蛋白激酶C在神经可塑性事件中的作用，我们研究了在给予AMPA后的不同时间，其α、β（I、II）和γ亚型（分别位于突触前和突触后）在听觉神经元中的表达情况。在未处理的耳蜗中，我们观察到初级听觉神经元的细胞体中存在PKCα、β（I、II）和γ的表达。在耳蜗内给予AMPA后，这两种同工酶均短暂过表达，在3 - 6小时达到峰值，随后在约24小时后下降。此时免疫电子显微镜显示一些再生的树突对PKCγ呈免疫反应性。给予AMPA五天后，当听觉反应恢复时，神经节细胞体中的PKCγ水平仍然升高。
