title: Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice.
abstract: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that negatively regulates autophagy. Rapamycin, an inhibitor of mTOR signaling, can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system (CNS). In the present study, we examined whether rapamycin treatment promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin significantly decreased the phosphorylation of the p70S6K protein and led to higher expression levels of LC3 and Beclin 1 in the injured spinal cord. In addition, neuronal loss and cell death in the injured spinal cord were significantly reduced in the rapamycin-treated mice compared to the vehicle-treated mice. Furthermore, the rapamycin-treated mice showed significantly higher locomotor function in Basso Mouse Scale (BMS) scores than did the vehicle-treated mice. These results indicate that rapamycin promoted autophagy by inhibiting the mTOR signaling pathway, and reduced neural tissue damage and locomotor impairment after SCI. The administration of rapamycin produced a neuroprotective function at the lesion site following SCI. Rapamycin treatment may represent a novel therapeutic strategy after SCI.
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sekiguchi
authors.forename: Haruo
authors.initials: H
authors.lastname: Kanno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaya
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D020123:Sirolimus