Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.
Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.
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DOI：
10.1016/j.celrep.2016.03.028
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发表时间：
2016-04-12
期刊：
影响因子：
8.8
通讯作者：
Zheng B
中科院分区：
文献类型：
--
作者：
Geoffroy CG;Hilton BJ;Tetzlaff W;Zheng B
中枢神经系统(CNS)损伤后，衰老如何影响轴突再生尚不清楚。我们评估了年龄对由Pten缺失诱导的皮质脊髓和红核脊髓神经元轴突再生的影响，这两种神经元具有不同的先天再生能力。与年轻小鼠一样，老年小鼠的Pten缺失仍然有效地防止脊髓损伤附近的mTOR活性、神经元胞体大小和轴突生长情况导致的神经内源性生长状态的下降。然而，损伤远端的轴突再生大大减少，伴随着损伤部位星形胶质细胞和炎症标志物的表达增加。因此，哺乳动物的中枢神经系统经历了轴突再生的年龄依赖性下降，当神经元的内在生长状态提高时就被揭示出来。这些结果对于制定促进中枢神经系统损伤或疾病后轴突修复的策略具有重要意义，中枢神经系统损伤或疾病日益影响中老年人口。
How aging impacts axon regeneration after central nervous system (CNS) injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations.
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