PTEN deletion enhances the regenerative ability of adult corticospinal neurons

Kai Liu, Yi Lu, Jae K. Lee, Ramsey Samara, Rafer Willenberg, Ilse Sears-Kraxberger, Andrea Tedeschi, Kevin Kyungsuk Park, Duo Jin, Bin Cai, Bengang Xu, Lauren Connolly, Oswald Steward, Binhai Zheng, Zhigang He

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Abstract

Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.

Original languageEnglish (US)
Pages (from-to)1075-1081
Number of pages7
JournalNature Neuroscience
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2010

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Liu, K., Lu, Y., Lee, J. K., Samara, R., Willenberg, R., Sears-Kraxberger, I., Tedeschi, A., Park, K. K., Jin, D., Cai, B., Xu, B., Connolly, L., Steward, O., Zheng, B., & He, Z. (2010). PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nature Neuroscience, 13(9), 1075-1081. https://doi.org/10.1038/nn.2603