Abstract
In multiple sclerosis (MS), long-term disability is primarily caused by axonal and neuronal damage. We demonstrated in a previous study that neuronal apoptosis occurs early during experimental autoimmune encephalomyelitis, a common animal model of MS. In the present study, we show that, in rats suffering from myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application of erythropoietin (Epo) significantly increased survival and function of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. We identified three independent intracellular signaling pathways involved in Epo-induced neuroprotection in vivo: Protein levels of phospho-Akt, phospho-MAPK 1 and 2, and Bcl-2 were increased under Epo application. Using a combined treatment of Epo together with a selective inhibitor of phosphatidylinositol 3-kinase (PI3-K) prevented upregulation of phospho-Akt and consecutive RGC rescue. We conclude that in MOG-EAE the PI3-K/Akt pathway has an important influence on RGC survival under systemic treatment with Epo.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis / drug effects
-
Apoptosis / physiology
-
Caspases / drug effects
-
Caspases / metabolism
-
Cell Count
-
Cell Survival / drug effects
-
Cell Survival / physiology
-
Disease Models, Animal
-
Electroretinography
-
Erythropoietin / administration & dosage
-
Erythropoietin / pharmacology*
-
Female
-
In Situ Nick-End Labeling / methods
-
Multiple Sclerosis / drug therapy*
-
Multiple Sclerosis / physiopathology
-
Myelin Proteins
-
Myelin-Associated Glycoprotein / administration & dosage
-
Myelin-Associated Glycoprotein / pharmacology*
-
Myelin-Oligodendrocyte Glycoprotein
-
Neuroprotective Agents / administration & dosage
-
Neuroprotective Agents / pharmacology*
-
Optic Nerve / physiopathology
-
Phosphorylation
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Proto-Oncogene Proteins / antagonists & inhibitors
-
Proto-Oncogene Proteins c-akt
-
Rats
-
Rats, Inbred BN
-
Recombinant Proteins / administration & dosage
-
Recombinant Proteins / pharmacology
-
Retinal Ganglion Cells / drug effects*
-
Retinal Ganglion Cells / physiology
-
Signal Transduction / drug effects
-
Signal Transduction / physiology*
Substances
-
Mog protein, rat
-
Myelin Proteins
-
Myelin-Associated Glycoprotein
-
Myelin-Oligodendrocyte Glycoprotein
-
Neuroprotective Agents
-
Proto-Oncogene Proteins
-
Recombinant Proteins
-
Erythropoietin
-
Akt1 protein, rat
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt
-
Caspases