Blond McIndoe Laboratories, University of Manchester, 3.106 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Exp Brain Res. 2012 Sep;221(4):357-67. doi: 10.1007/s00221-012-3179-4. Epub 2012 Jul 24.
Peripheral nerve injuries (PNI) are continuing to be an ever-growing socio-economic burden affecting mainly the young working population and the current clinical treatments to PNI provide a poor clinical outcome involving significant loss of sensation. Thus, our understanding of the underlying factors responsible for the extensive loss of the sensory cutaneous subpopulation in the dorsal root ganglia (DRG) that occurs following injury needs to be improved. The current investigations focus in identifying visual cues of mitochondria-related apoptotic events in the various subpopulations of sensory cutaneous neurons. Sensory neuronal subpopulations were identified using FastBlue retrograde labelling following axotomy. Specialised fluorogenic probes, MitoTracker Red and MitoTracker Orange, were employed to visualise the dynamic changes of the mitochondrial population of neurons. The results reveal a fragmented mitochondrial network in sural neurons following apoptosis, whereas a fused elongated mitochondrial population is present in sensory proprioceptive muscle neurons following tibial axotomy. We also demonstrate the neuroprotective properties of NAC and ALCAR therapy in vitro. The dynamic mitochondrial network breaks down following oxidative exposure to hydrogen peroxide (H(2)O(2)), but reinitiates fusion after NAC and ALCAR therapy. In conclusion, this study provides both qualitative and quantitative evidence of the susceptibility of sensory cutaneous sub-population in apoptosis and of the neuroprotective effects of NAC and ALCAR treatment on H(2)O(2)-challenged neurons.
周围神经损伤(PNI)不断成为日益增长的社会经济负担,主要影响年轻的劳动人口,目前 PNI 的临床治疗效果不佳,导致感觉明显丧失。因此,我们需要更好地了解导致损伤后背根神经节(DRG)中感觉皮肤亚群大量丢失的潜在因素。目前的研究集中在确定与线粒体相关的凋亡事件在感觉皮肤神经元的各种亚群中的视觉线索。感觉神经元亚群在轴突切断后通过逆行标记 FastBlue 进行鉴定。使用专门的荧光探针 MitoTracker Red 和 MitoTracker Orange 来可视化神经元线粒体群体的动态变化。结果显示,在凋亡后腓肠神经元中存在线粒体网络碎片化,而在胫骨轴突切断后感觉本体感受肌神经元中存在融合的延长线粒体群体。我们还在体外证明了 NAC 和 ALCAR 治疗的神经保护特性。暴露于过氧化氢(H 2 O 2 )后,动态线粒体网络会发生断裂,但在用 NAC 和 ALCAR 治疗后会重新开始融合。总之,这项研究提供了感觉皮肤亚群在凋亡中易感性的定性和定量证据,以及 NAC 和 ALCAR 治疗对 H 2 O 2 挑战神经元的神经保护作用。