Erythropoietin receptor is expressed on adult rat dopaminergic neurons and erythropoietin is neurotrophic in cultured dopaminergic neuroblasts.
Exogenous erythropoietin (EPO) is a potent neurotrophic factor in vivo, protective against neuronal death in animal models of brain ischemia and human stroke. To date, reports on the distribution of EPO receptor in brain suggest that it is expressed mostly on capillaries. This receptor pattern suggests an indirect effect of EPO on neurons. In these studies, we show that EPO receptor is abundantly expressed on adult dopaminergic neurons, suggesting a direct effect of EPO on neurons. Furthermore, we show that EPO mediates the classic neurotrophic effects of proliferation, differentiation and maintenance in a dopaminergic cell line. The biology of therapeutically administered EPO in brain is a function of its receptor distribution, and the neuronal expression of EPO receptor on adult CNS neurons is consistent with EPO's potent neurotrophic function in vivo.
Csete
Marie
M
Department of Anesthesiology, Program in Neurosciences, Emory University School of Medicine, Research Labs, 1462 Clifton Road NE, Room 420, Atlanta, GA 30322, USA. marie_csete@emoryhealthcare.org
Rodriguez
Luis
L
Wilcox
Melissa
M
Chadalavada
Seetharam
S
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000096:biosynthesis* / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D009414:Nerve Growth Factors; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D004298:Dopamine