PTEN deletion enhances the regenerative ability of adult corticospinal neurons

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

Research output: Contribution to journalArticle

503 Citations (Scopus)

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

Fingerprint

Pyramidal Tracts
Axons
Neurons
Regeneration
Spinal Cord
Wounds and Injuries
Spinal Cord Injuries
Synapses
Up-Regulation
Down-Regulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Liu, K., Lu, Y., Lee, J., Samara, R., Willenberg, R., Sears-Kraxberger, I., ... 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

PTEN deletion enhances the regenerative ability of adult corticospinal neurons. / Liu, Kai; Lu, Yi; Lee, Jae; Samara, Ramsey; Willenberg, Rafer; Sears-Kraxberger, Ilse; Tedeschi, Andrea; Park, Kevin; Jin, Duo; Cai, Bin; Xu, Bengang; Connolly, Lauren; Steward, Oswald; Zheng, Binhai; He, Zhigang.

In: Nature Neuroscience, Vol. 13, No. 9, 01.09.2010, p. 1075-1081.

Research output: Contribution to journalArticle

Liu, K, Lu, Y, Lee, J, Samara, R, Willenberg, R, Sears-Kraxberger, I, Tedeschi, A, Park, 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, vol. 13, no. 9, pp. 1075-1081. https://doi.org/10.1038/nn.2603
Liu K, Lu Y, Lee J, Samara R, Willenberg R, Sears-Kraxberger I et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nature Neuroscience. 2010 Sep 1;13(9):1075-1081. https://doi.org/10.1038/nn.2603
Liu, Kai ; Lu, Yi ; Lee, Jae ; Samara, Ramsey ; Willenberg, Rafer ; Sears-Kraxberger, Ilse ; Tedeschi, Andrea ; Park, Kevin ; Jin, Duo ; Cai, Bin ; Xu, Bengang ; Connolly, Lauren ; Steward, Oswald ; Zheng, Binhai ; He, Zhigang. / PTEN deletion enhances the regenerative ability of adult corticospinal neurons. In: Nature Neuroscience. 2010 ; Vol. 13, No. 9. pp. 1075-1081.
@article{0370f5e6ed2c4461b1a4dc4409ff1114,
title = "PTEN deletion enhances the regenerative ability of adult corticospinal neurons",
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.",
author = "Kai Liu and Yi Lu and Jae Lee and Ramsey Samara and Rafer Willenberg and Ilse Sears-Kraxberger and Andrea Tedeschi and Kevin Park and Duo Jin and Bin Cai and Bengang Xu and Lauren Connolly and Oswald Steward and Binhai Zheng and Zhigang He",
year = "2010",
month = "9",
day = "1",
doi = "10.1038/nn.2603",
language = "English",
volume = "13",
pages = "1075--1081",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - PTEN deletion enhances the regenerative ability of adult corticospinal neurons

AU - Liu, Kai

AU - Lu, Yi

AU - Lee, Jae

AU - Samara, Ramsey

AU - Willenberg, Rafer

AU - Sears-Kraxberger, Ilse

AU - Tedeschi, Andrea

AU - Park, Kevin

AU - Jin, Duo

AU - Cai, Bin

AU - Xu, Bengang

AU - Connolly, Lauren

AU - Steward, Oswald

AU - Zheng, Binhai

AU - He, Zhigang

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956187905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956187905&partnerID=8YFLogxK

U2 - 10.1038/nn.2603

DO - 10.1038/nn.2603

M3 - Article

C2 - 20694004

AN - SCOPUS:77956187905

VL - 13

SP - 1075

EP - 1081

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 9

ER -