Brimonidine promotes axon growth after optic nerve injury through Erk phosphorylation.
It is well known that axons of the adult mammalian central nervous system have a very limited ability to regenerate after injury. Therefore, the neurodegenerative process of glaucoma results in irreversible functional deficits, such as blindness. Brimonidine (BMD) is an alpha2-adrenergic receptor agonist that is used commonly to lower intraocular pressure in glaucoma. Although it has been suggested that BMD has neuroprotective effects, the underlying mechanism remains unknown. In this study, we explored the molecular mechanism underlying the neuroprotective effect of BMD in an optic nerve injury (ONI) model. BMD treatment promoted optic nerve regeneration by inducing Erk1/2 phosphorylation after ONI. In addition, an Erk1/2 antagonist suppressed BMD-mediated axonal regeneration. A gene expression analysis revealed that the expression of the neurotrophin receptor gene p75 was increased and that the expression of the tropomyosin receptor kinase B (TrkB) gene was decreased after ONI. BMD treatment abrogated the changes in the expression of these genes. These results indicate that BMD promotes optic nerve regeneration via the activation of Erk1/2.
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Osaka, Japan.
Y
Y
Fujita
A
A
Sato
T
T
Yamashita
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D000068438:Brimonidine Tartrate; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D020221:Optic Nerve Injuries / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects
D018696:Neuroprotective Agents; D011810:Quinoxalines; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D000068438:Brimonidine Tartrate; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt