Activation of MAPK and CREB by GM1 induces survival of RGCs in the retina with axotomized nerve.
OBJECTIVE
Neuronal cells undergo apoptosis when the supply of neurotrophic factor is limited by injury, trauma, or neurodegenerative disease. Ganglioside has both neuritogenic and neurotropic functions. Exogenously administered monosialoganglioside (GM1) has been shown to have a stimulatory effect on neurite outgrowth and to prevent degeneration of neuronal cells in the central nervous system. Even though GM1 has been shown to mimic, or have synergy with, neurotrophic factors, the neuroprotective mechanism of GM1 has not been well understood. In this study, optic nerve transection, or axotomy, was used as an in vivo model system for injury, to examine the protective mechanism of GM1 in injured retinal ganglion cells.


METHODS
GM1 was injected into the vitreous body before axotomy, and the protective effect of GM1 observed with regard to activation of mitogen-activated protein kinase (MAPK) and phosphorylation of cAMP-responsive element-binding (CREB) protein. Activation of MAPK and CREB were examined by Western blot analysis and immunohistochemistry, and the surviving retinal ganglion cells were counted after retrograde fluorescence labeling.


RESULTS
GM1 inhibited the degeneration of axotomized retinal ganglion cells. In addition, GM1 enhanced the activation of MAPK and CREB with the treatment of GM1 in the retina with axotomized nerve. Treatment of MAPK inhibitor PD98059 with GM1 reduced the protective action of GM1 and prevented GM1-induced phosphorylation of CREB.


CONCLUSIONS
GM1 protected the axotomized retinal ganglion cells (RGCs) from cell death after axotomy through the activation of MAPK and CREB.
Choi
Jun-Sub
JS
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Jeong-A
JA
Joo
Choun-Ki
CK
D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004789:Enzyme Activation; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009900:Optic Nerve / Q000601:surgery; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D005677:G(M1) Ganglioside; D020928:Mitogen-Activated Protein Kinases