Estradiol promotes proliferation of dopaminergic precursors resulting in a higher proportion of dopamine neurons derived from mouse embryonic stem cells.
Estradiol protects dopamine neurons of the substantia nigra from toxic insults. Such neurons succumb in Parkinson's disease; one strategy for restoring dopamine deficiency is cell therapy with neurons differentiated from embryonic stem cells. We investigated the effects of 17beta-estradiol on dopaminergic induction of embryonic stem cells using the 5-stage protocol. Cells were incubated with different steroid concentrations during the proliferation (stage 4) or differentiation (stage 5) phases. Estradiol added at nM concentrations only during stage 4 increases the proliferation of dopaminergic precursors expressing Lmx1a, inducing a higher proportion of dopamine neurons at stage 5. These actions were mediated by activation of estrogen receptors, because co-incubation of cells with estradiol and ICI 182,780 completely abolished the positive effect on both proliferation of committed precursors, and subsequent differentiation to dopaminergic neurons. Our results suggest that estradiol should be useful in producing higher proportions of dopamine neurons from embryonic stem cells aimed for treating Parkinson's disease.
Díaz
Néstor F
NF
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico.
Díaz-Martínez
Néstor E
NE
Camacho-Arroyo
Ignacio
I
Velasco
Iván
I
D000818:Animals; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D004958:Estradiol / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D000099153:Pentraxins
D002097:C-Reactive Protein; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D004958:Estradiol; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051096:Proto-Oncogene Proteins c-ret; D014157:Transcription Factors; D000099153:Pentraxins; C489692:Lmx1a protein, mouse