Oliveira Alexandre L R, Risling Mårten, Negro Alessandro, Langone Francesco, Cullheim Staffan
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Comp Neurol. 2002 Jun 10;447(4):381-93. doi: 10.1002/cne.10248.
We have previously shown that not only motoneurons and dorsal root ganglion cells but also small neurons, presumably interneurons in the spinal cord, may undergo apoptotic cell death as a result of neonatal peripheral nerve transection in the rat. With the aid of electron microscopy, we have here demonstrated that apoptosis in the spinal cord is confined to neurons and does not involve glial cells at the survival time studied (24 hours). To define the relative importance of the loss of a potential target (motoneuron) and a potential afferent input (dorsal root ganglion cell) for the induction of apoptosis in interneurons in this situation, we have compared the distributions and time courses for TUNEL labeling, which detects apoptotic cell nuclei, in the L5 segment of the spinal cord and the L5 dorsal root ganglion after sciatic nerve transection in the neonatal (P2) rat. In additional experiments, we studied the effects on TUNEL labeling of interneurons after treatment of the cut sciatic nerve with either ciliary neurotrophic factor (CNTF) to rescue motoneurons or nerve growth factor (NGF) to rescue dorsal root ganglion cells. The time courses of the TUNEL labeling in motoneurons and interneurons induced by the lesion show great similarities (peak at 8-48 hours postoperatively), whereas the labeling in dorsal root ganglion cells occurs later (24-72 hours). Both CNTF and NGF decrease the number of TUNEL-labeled interneurons, but there is a regional difference, in that CNTF preferentially saves interneurons in deep dorsal and ventral parts of the spinal cord, whereas the rescuing effects of NGF are seen mainly in the superficial dorsal horn. The results are interpreted as signs of a trophic dependence on both the target and the afferent input for the survival of interneurons neonatally.
我们之前已经表明，不仅运动神经元和背根神经节细胞，而且脊髓中的小神经元（推测为中间神经元），可能会因新生大鼠的外周神经横断而发生凋亡性细胞死亡。借助电子显微镜，我们在此证明，在所研究的存活时间（24小时），脊髓中的凋亡仅限于神经元，不涉及神经胶质细胞。为了确定在这种情况下，潜在靶标（运动神经元）丧失和潜在传入输入（背根神经节细胞）丧失对中间神经元凋亡诱导的相对重要性，我们比较了新生（P2）大鼠坐骨神经横断后，脊髓L5节段和L5背根神经节中检测凋亡细胞核的TUNEL标记的分布和时间进程。在额外的实验中，我们研究了用睫状神经营养因子（CNTF）挽救运动神经元或用神经生长因子（NGF）挽救背根神经节细胞后，对中间神经元TUNEL标记的影响。损伤诱导的运动神经元和中间神经元中TUNEL标记的时间进程显示出很大的相似性（术后8 - 48小时达到峰值），而背根神经节细胞中的标记出现得较晚（24 - 72小时）。CNTF和NGF都减少了TUNEL标记的中间神经元数量，但存在区域差异，即CNTF优先挽救脊髓深部背侧和腹侧的中间神经元，而NGF的挽救作用主要见于浅表背角。这些结果被解释为新生中间神经元的存活对靶标和传入输入都存在营养依赖性的迹象。
