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.
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.forename: Ramsey
authors.initials: R
authors.lastname: Samara
authors.forename: Rafer
authors.initials: R
authors.lastname: Willenberg
authors.forename: Ilse
authors.initials: I
authors.lastname: Sears-Kraxberger
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Kevin Kyungsuk
authors.initials: KK
authors.lastname: Park
authors.forename: Duo
authors.initials: D
authors.lastname: Jin
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Bengang
authors.initials: B
authors.lastname: Xu
authors.forename: Lauren
authors.initials: L
authors.lastname: Connolly
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
authors.forename: Binhai
authors.initials: B
authors.lastname: Zheng
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002574:Cervical Vertebrae; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008526:Medulla Oblongata / Q000502:physiology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011712:Pyramidal Tracts / Q000502:physiology* / Q000503:physiopathology / Q000648:ultrastructure; D013003:Somatosensory Cortex / Q000502:physiology / Q000503:physiopathology; D013116:Spinal Cord / Q000502:physiology / Q000503:physiopathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000503:physiopathology; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D058570:TOR Serine-Threonine Kinases; D013904:Thoracic Vertebrae
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse