Yamada Jun, Hayashi Yoshinori, Jinno Shozo, Wu Zhou, Inoue Kazuhide, Kohsaka Shinichi, Nakanishi Hiroshi
Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Glia. 2008 Oct;56(13):1448-62. doi: 10.1002/glia.20711.
Activated microglia, which spread on the motor neurons following nerve injury, engage in the displacement of detached afferent synaptic boutons from the surface of regenerating motor neurons. This phenomenon is known as "synaptic stripping." The present study attempted to examine whether changes in the synaptic inputs after motor nerve injury correlated with the microglial attachment to the dorsal motor neurons of the vagus (DMV). DMV neurons in Wistar rats could survive after nerve injury, whereas most of injured DMV neurons in the C57BL/6 mice died. At 2 days after nerve injury, a significant decrease was observed in the frequencies of both spontaneous and miniature EPSCs and IPSCs recorded from DMV neurons in the slice preparation but not from the mechanically dissociated neurons in the Wistar rats. At this stage, no direct apposition of microglia on the injured neurons was observed. High-K(+) stimulation restored their frequencies to control levels. Furthermore, PPADS and DPCPX, antagonists of P2 and adenosine receptors, respectively, also stimulated the recovery of their frequencies. In contrast, no significant change was detected in the spontaneous EPSCs frequency recorded from the severely injured DMV neurons in the slice preparation of the C57BL/6 mice. These observations strongly suggest that presynaptic inhibition through glia-derived ATP and adenosine, thus precedes synaptic stripping in regenerating DMV neurons following nerve injury.
活化的小胶质细胞在神经损伤后会扩散到运动神经元上,参与将分离的传入突触小体从再生运动神经元表面移开。这种现象被称为“突触剥离”。本研究试图检验运动神经损伤后突触输入的变化是否与小胶质细胞与迷走神经背运动核(DMV)的附着有关。Wistar大鼠的DMV神经元在神经损伤后能够存活,而C57BL/6小鼠中大多数受损的DMV神经元死亡。在神经损伤后2天,在切片制备中从DMV神经元记录到的自发和微小兴奋性突触后电流(EPSC)以及抑制性突触后电流(IPSC)的频率均显著降低,但在Wistar大鼠的机械分离神经元中未出现这种情况。在此阶段,未观察到小胶质细胞直接附着在受损神经元上。高钾刺激将它们的频率恢复到对照水平。此外,P2和腺苷受体的拮抗剂PPADS和DPCPX也分别刺激了它们频率的恢复。相比之下,在C57BL/6小鼠切片制备中从严重受损的DMV神经元记录到的自发EPSC频率未检测到显著变化。这些观察结果强烈表明,在神经损伤后再生的DMV神经元中,通过胶质细胞衍生的ATP和腺苷进行的突触前抑制先于突触剥离。