Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury

• Published in: Cell death & disease Vol. 4; no. 4; p. e567
• Main Authors: Tanaka, T, Fujita, Y, Ueno, M, Shultz, L D, Yamashita, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2013; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/378/1687; 692/699/375/1345; Animals; Antibodies; Axons - drug effects; Axons - physiology; Biochemistry; Biomedical and Life Sciences; Brain Injuries - drug therapy; Brain Injuries - metabolism; Cell Biology; Cell Culture; Down-Regulation; Enzyme Inhibitors - pharmacology; Forelimb - drug effects; Forelimb - physiology; Heterozygote; Immunology; Life Sciences; Male; Mice; Motor Cortex - drug effects; Motor Cortex - injuries; Motor Cortex - physiology; Nerve Fibers - drug effects; Nerve Fibers - physiology; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Original; original-article; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - deficiency; Pyramidal Tracts - drug effects; Pyramidal Tracts - enzymology; Pyramidal Tracts - injuries; Quinolines - pharmacology; Recovery of Function; axonal sprouting; brain injury; SHP-1; functional recovery; corticospinal tract
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2013.102

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.