BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons.
Olfactory ensheathing cells (OECs) are the main glial cell type that populates mammalian olfactory nerves. These cells have a great capacity to promote the regeneration of axons when transplanted into the injured adult mammalian CNS. However, little is still known about the molecular mechanisms they employ in mediating such a task. Brain-derived neurotrophic factor (BDNF) was identified as a candidate molecule in a genomic study that compared three functionally different OEC populations: Early passage OECs (OEC Ep), Late passage OECs (OEC Lp) and the OEC cell line TEG3 [Pastrana, E., Moreno-Flores, M.T., Gurzov, E.N., Avila, J., Wandosell, F., Diaz-Nido, J., 2006. Genes associated with adult axon regeneration promoted by olfactory ensheathing cells: a new role for matrix metalloproteinase 2. J. Neurosci. 26, 5347-5359]. We have here set out to determine the role played by BDNF in the stimulation of axon outgrowth by OECs. We compared the extracellular BDNF levels in the three OEC populations and show that it is produced in significant amounts by the OECs that can stimulate axon regeneration in adult retinal neurons (OEC Ep and TEG3) but it is absent from the extracellular medium of OEC Lp cells which lack this capacity. Blocking BDNF signalling impaired axonal regeneration of adult retinal neurons co-cultured with TEG3 cells and adding BDNF increased the proportion of adult neurons that regenerate their axons on OEC Lp monolayers. Combining BDNF with other extracellular proteins such as Matrix Metalloproteinase 2 (MMP2) further augmented this effect. This study shows that BDNF production by OECs plays a direct role in the promotion of axon regeneration of adult CNS neurons.
Pastrana
Erika
E
Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Madrid, Spain.
Moreno-Flores
Maria Teresa
MT
Avila
Jesus
J
Wandosell
Francisco
F
Minichiello
Liliana
L
Diaz-Nido
Javier
J
D000818:Animals; D001369:Axons; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D051381:Rats; D012038:Regeneration
D019208:Brain-Derived Neurotrophic Factor