Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord.
Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord.
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作者：
Zhai J;Kim H;Han SB;Manire M;Yoo R;Pang S;Smith GM;Son YJ
背根(DR)损伤后脊髓内再生的一个主要障碍是DR进入区(DREZ)，即CNS/PNS界面。DR轴突在DREZ停止再生，即使神经条件性损伤增加了再生能力。长期以来，这种有效的阻断一直被归因于髓鞘相关抑制剂和(CSPGs)，但不完全的损害和相互矛盾的报告阻碍了最终的一致意见。在这里，我们使用新的策略来评估小鼠的DR再生，以促进完整的损伤和分析，选择性追踪本体感觉和机械感受性轴突，以及第一次同时靶向Nogo/网状蛋白-4、MAG、OMGp、CSPGs和GDNF。共同消除髓鞘抑制物和CSPG只诱导了DREZ中少数条件性损伤的DR轴突的再生。然而，它们的缺乏显著和协同地促进了GDNF刺激的轴突的再生，突显了充分提高内在生长能力的重要性。我们还得出结论，髓鞘抑制剂和CSPG不是阻止DRIZ轴突的主要机制。
A major barrier to intraspinal regeneration after dorsal root (DR) injury is the DR entry zone (DREZ), the CNS/PNS interface. DR axons stop regenerating at the DREZ, even if regenerative capacity is increased by a nerve conditioning lesion. This potent blockade has long been attributed to myelin-associated inhibitors and (CSPGs), but incomplete lesions and conflicting reports have prevented conclusive agreement. Here, we evaluated DR regeneration in mice using novel strategies to facilitate complete lesions and analyses, selective tracing of proprioceptive and mechanoreceptive axons, and the first simultaneous targeting of Nogo/Reticulon-4, MAG, OMgp, CSPGs, and GDNF. Co-eliminating myelin inhibitors and CSPGs elicited regeneration of only a few conditioning-lesioned DR axons across the DREZ. Their absence, however, markedly and synergistically enhanced regeneration of GDNF-stimulated axons, highlighting the importance of sufficiently elevating intrinsic growth capacity. We also conclude that myelin inhibitors and CSPGs are not the primary mechanism stopping axons at the DREZ.
影响因子：
5.3
作者：
Kelamangalath, Lakshmi;Tang, Xiaoqing;Bezik, Kathleen;Sterling, Noelle;Son, Young-Jin;Smith, George M.
通讯作者：
Smith, George M.