title: Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury.
abstract: Reorganization of spared neural network connections is one of the most important processes for restoring impaired function after brain injury. However, plasticity is quite limited in the adult brain due to the presence of inhibitory molecules and a lack of intrinsic neuronal signals for axonal growth. Src homology 2-containing phosphatase (SHP)-1 has been shown to have a role in axon growth inhibition. Here, we tested the hypothesis that SHP-1 negatively affects axonal reorganization. We observed that unilateral motor cortex injury led to increased expression and activity of SHP-1 in the contralesional cortex. In this model, corticospinal axons originating from the contralesional cortex sprouted into the denervated side of the cervical spinal cord after injury. We observed that the number of sprouting fibers was increased in SHP-1-deficient heterozygous viable motheaten (+/me(v)) mice, which show reduced SHP-1 activity, and in wild-type mice treated with an SHP inhibitor. Motor function recovery of impaired forelimb was enhanced in +/me(v) mice. Collectively, our results indicate that downregulation of SHP-1 activity promotes corticospinal tract sprouting and functional recovery after brain injury.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005552:Forelimb / Q000187:drug effects / Q000502:physiology; D006579:Heterozygote; D008297:Male; D051379:Mice; D009044:Motor Cortex / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors* / Q000172:deficiency; D011712:Pyramidal Tracts / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D011804:Quinolines / Q000494:pharmacology*; D020127:Recovery of Function
chemical_list: D004791:Enzyme Inhibitors; C512715:NSC-87877; D011804:Quinolines; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse
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