title: Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.
abstract: Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats. We have found that unilateral sciatic nerve transection results in the elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the contralateral side, commonly considered as a control. Bilateral transection further increased NGF but not other neurotrophins in the nerve segment distal to the transection site, as compared to the unilateral injury. To further investigate the distinct role of NGF in regeneration and its potential for peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding lentivirus and transplanted the over-expressing cells into the distal segment of a transected nerve. Axonal regeneration was studied at 2 weeks time-point using pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the regenerating nerve.
authors.affiliation: Department of Clinical Neuroscience, Faculty of Medicine, University of Calgary, Calgary, Canada. shakhbazau@gmail.com
authors.forename: Antos
authors.initials: A
authors.lastname: Shakhbazau
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martinez
authors.forename: Qing-Gui
authors.initials: QG
authors.lastname: Xu
authors.forename: Jean
authors.initials: J
authors.lastname: Kawasoe
authors.forename: Jan
authors.initials: J
authors.lastname: van Minnen
authors.forename: Rajiv
authors.initials: R
authors.lastname: Midha
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000378:metabolism / Q000637:transplantation; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D014185:Transplantation, Isogeneic / Q000379:methods
chemical_list: D016900:Neurofilament Proteins; D020933:Neurotrophin 3; C051774:neurofilament protein H; D020932:Nerve Growth Factor