title: The role of the PI3K/Akt/mTOR pathway in glial scar formation following spinal cord injury.
abstract: Several studies suggest that glial scars pose as physical and chemical barriers that limit neurite regeneration after spinal cord injury (SCI). Evidences suggest that the activation of the PI3K/Akt/mTOR signaling pathway is involved in glial scar formation. Therefore, inhibition of the PI3K/Akt/mTOR pathway may beneficially attenuate glial scar formation after SCI. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates the PI3K/Akt/mTOR pathway. Therefore, we hypothesized that the overexpression of PTEN in the spinal cord will have beneficial effects after SCI. In the present study, we intrathecally injected a recombinant adenovirus carrying the pten gene (Ad-PTEN) to cause overexpression of PTEN in rats with contusion injured spinal cords. The results suggest overexpression of PTEN in spinal cord attenuated glial scar formation and led to improved locomotor function after SCI. Overexpression of PTEN following SCI attenuated gliosis, affected chondroitin sulfate proteoglycan expression, and improved axon regeneration into the lesion site. Furthermore, we suggest that the activation of the PI3K/Akt/mTOR pathway in astrocytes at 3 days after SCI may be involved in glial scar formation. Because delayed treatment with Ad-PTEN enhanced motor function recovery more significantly than immediate treatment with Ad-PTEN after SCI, the results suggest that the best strategy to attenuate glial scar formation could be to introduce 3 days after SCI. This study's findings thus have positive implications for patients who are unable to receive immediate medical attention after SCI.
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung, Taiwan.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Sung
authors.initials: CS
authors.lastname: Sung
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Feng
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung, Taiwan.
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Hung
authors.affiliation: I-Shou University, School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, Kaohsiung, Taiwan.
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.affiliation: Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Nan-Fu
authors.initials: NF
authors.lastname: Chen
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: wzh@mail.com.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: ma4949@adm.cgmh.org.tw.
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020123:Sirolimus
keywords: Astrocyte; Chondroitin sulfate proteoglycans; Glial scar; Phosphatase and tensin homolog deleted on chromosome 10