Abstract

The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon‐regrowth, we analyzed cell growth control genes using a virus‐assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathway, in adult retinal ganglion cells (RGCs) promotes robust axon regeneration after optic nerve injury. In wild‐type adult mice, the mTOR activity was suppressed and new protein synthesis was impaired in axotomized RGCs, which may contribute to the regeneration failure. Reactivating this pathway by conditional knockout of tuberous sclerosis complex 1 (TSC1), another negative regulator of the mTOR pathway, also leads to axon regeneration. Thus, our results suggest the manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration following CNS injury.

Highlights

  • Spinal cord injury disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site

  • Rebuilding the functional circuits may result from two types of axon regrowth: 1 true regenerative growth of injured axons and 2 compensatory sprouting from spared fibers

  • Several myelin associated molecules and chondroitin sulfate proteoglycans (CSPGs) in the glial scar have been implicated as inhibitors of axon regeneration[2,3,4,5,6,7]

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Summary

Published Version Citable link Terms of Use

He, Zhigang. 2010. Intrinsic control of axon regeneration. Journal of Biomedical Research 24(1): 2-5. doi:10.1016/S1674-8301(10)60002-4 http://nrs.harvard.edu/urn-3:HUL.InstRepos:11180996 This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-ofuse#LAA

Zhigang He*
Injury to the mammalian adult central nervous
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