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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Artemin promotes functional long-distance axonal regeneration to the brainstem after dorsal root crush
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Artemin promotes functional long-distance axonal regeneration to the brainstem after dorsal root crush

机译:Artemin promotes functional long-distance axonal regeneration to the brainstem after dorsal root crush

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摘要

Recovery after a spinal cord injury often requires that axons restore synaptic connectivity with denervated targets several centimeters from the site of injury. Here we report that systemic artemin (ARTN) treatment promotes the regeneration of sensory axons to the brainstem after brachial dorsal root crush in adult rats. ARTN not only stimulates robust regeneration of large, myelinated sensory axons to the brainstem, but also promotes functional reinnervation of the appropriate target region, the cuneate nucleus. ARTN signals primarily through the RET tyrosine kinase, an interaction that requires the nonsignaling coreceptor GDNF family receptor (GFR alpha 3). Previous studies reported limited GFR alpha 3 expression on large sensory neurons, but our findings demonstrate that ARTN promotes robust regeneration of large, myelinated sensory afferents. Using a cell sorting technique, we demonstrate that GFR alpha 3 expression is similar in myelinated and unmyelinated adult sensory neurons, suggesting that ARTN likely induces long-distance regeneration by binding GFR alpha 3 and RET. Although ARTN is delivered for just 2 wk, regeneration to the brainstem requires more than 3 mo, suggesting that brief trophic support may initiate intrinsic growth programs that remain active until targets are reached. Given its ability to promote targeted functional regeneration to the brainstem, ARTN may represent a promising therapy for restoring sensory function after spinal cord injury.

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