The Effect of Axon Resealing on Retrograde Neuronal Death after Spinal Cord Injury in Lamprey.
The Effect of Axon Resealing on Retrograde Neuronal Death after Spinal Cord Injury in Lamprey.
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DOI：
10.3390/brainsci8040065
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发表时间：
2018-04-14
期刊：
影响因子：
3.3
通讯作者：
Selzer ME
中科院分区：
文献类型：
--
作者：
Zhang G;Rodemer W;Lee T;Hu J;Selzer ME
哺乳动物中枢神经系统(CNS)轴突再生的失败既有外源性抑制因素，也有神经元内源性因素。在七鳃鳗中，18对单独识别的大型网状脊髓(RS)神经元说明了内在因素的重要性，这些神经元的轴突位于同一脊髓束中，但在脊髓横断(TX)后再生能力差异很大。再生不良的神经元也会经历非常延迟的凋亡，caspase的激活很早就发出了信号。我们注意到，轴突再生概率较低的神经元往往比再生能力好的神经元大。我们推测，再生不良的较大神经元有较大口径的轴突，重新扫描速度较慢，允许有毒信号(例如，Ca++)更长时间地进入损伤部位的轴突。为了验证这一假设，我们使用了一种染料排斥试验，在TX后逐渐延长的时间间隔内，将不透膜染料应用于脊髓的断端。属于RS内侧下核极小神经元的轴突在TX后15分钟内重新封闭。几乎75%属于中型RS神经元的轴突在3小时内重新密封。此时，只有36%的最大轴突重新密封，通常需要超过24小时才能排除染料。RS神经元的大小与轴突再生概率呈负相关(r=−0.92)，荧光标记的半胱氨酸天冬氨酸酶抑制物染色显示，神经元发生迟发性凋亡的概率为0.73。在脊髓损伤(SCI)后2周，用聚乙二醇(PEG)人工加速再封闭可使逆行神经元的凋亡率减少69.5%，提示轴突再封闭是细胞存活的关键决定因素。无Ca~(++)Ringer‘s液加EGTA可延长封闭时间，增加细胞凋亡信号，提示除Ca~(++)扩散进入损伤尖端外，其他因素也参与了死亡信号的逆行传递。损伤离细胞体的距离越远，凋亡信号就越少，这与轴突封闭时间无关。
Failure of axon regeneration in the central nervous system (CNS) of mammals is due to both extrinsic inhibitory factors and to neuron-intrinsic factors. The importance of intrinsic factors is illustrated in the sea lamprey by the 18 pairs of large, individually identified reticulospinal (RS) neurons, whose axons are located in the same spinal cord tracts but vary greatly in their ability to regenerate after spinal cord transection (TX). The neurons that are bad regenerators also undergo very delayed apoptosis, signaled early by activation of caspases. We noticed that the neurons with a low probability of axon regeneration tend to be larger than the good regenerators. We postulate that the poorly regenerating larger neurons have larger caliber axons, which reseal more slowly, allowing more prolonged entry of toxic signals (e.g., Ca++) into the axon at the injury site. To test this hypothesis, we used a dye-exclusion assay, applying membrane-impermeable dyes to the cut ends of spinal cords at progressively longer post-TX intervals. Axons belonging to the very small neurons (not individually identified) of the medial inferior RS nucleus resealed within 15 min post-TX. Almost 75% of axons belonging to the medium-sized identified RS neurons resealed within 3 h. At this time, only 36% of the largest axons had resealed, often taking more than 24 h to exclude the dye. There was an inverse relationship between an RS neuron’s size and the probability that its axon would regenerate (r = −0.92) and that the neuron would undergo delayed apoptosis, as indicated by staining with a fluorescently labeled inhibitor of caspases (FLICA; r = 0.73). The artificial acceleration of resealing with polyethylene glycol (PEG) reduced retrograde neuronal apoptosis by 69.5% at 2 weeks after spinal cord injury (SCI), suggesting that axon resealing is a critical determinant of cell survival. Ca++-free Ringer’s solution with EGTA prolonged the sealing time and increased apoptotic signaling, suggesting that factors other than Ca++ diffusion into the injured tip contribute to retrograde death signaling. A longer distance of the lesion from the cell body reduced apoptotic signaling independent of the axon sealing time.
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DOI：
10.1073/pnas.83.8.2763
发表时间：
1986-04-01
影响因子：
11.1
作者：
COHEN, AH;MACKLER, SA;SELZER, ME
通讯作者：
SELZER, ME
影响因子：
2.5
作者：
Busch, David J.;Morgan, Jennifer R.
通讯作者：
Morgan, Jennifer R.
DOI：
10.1007/bf01206673
发表时间：
1979-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
CHRISTENSEN, BN;QUINN, J
通讯作者：
QUINN, J
影响因子：
14.5
作者：
BLIGHT, AR;COHEN, TI;HEYES, MP
通讯作者：
HEYES, MP
影响因子：
2.5
作者：
DAVIS, GR;MCCLELLAN, AD
通讯作者：
MCCLELLAN, AD