Abstract
Mesencephalic precursors derived from early (embryonic day 12; E12) rat embryos were grown in vitro using mitogen basic fibroblast growth factor (bFGF) and these cells efficiently differentiated into dopaminergic (DA) neurons. However, this in vitro DA differentiation was poor in mesencephalic precursors isolated from later embryos (E13-15). Ascorbate (AA) treatment enhanced yields of DA neurons from E12 precursors, and increased the number of DA neurons generated from E13 precursors to levels attained when using E12 precursors. AA markedly up-regulated expression of bone morphogenetic protein 7 (BMP7) and erythropoietin (Epo) in precursors, but did not affect expression of a number of genes known to regulate midbrain DA development. The addition of these recombinant proteins or blockers revealed that both BMP7 and Epo mediate AA-induced DA neuron differentiation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology*
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Ascorbic Acid / pharmacology*
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins / physiology*
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Cell Count
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Cell Differentiation / drug effects*
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Cells, Cultured
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Chromatography, High Pressure Liquid / instrumentation
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Chromatography, High Pressure Liquid / methods
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Dopamine
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Dopamine beta-Hydroxylase / metabolism
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Embryo, Mammalian
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Erythropoietin / physiology*
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Female
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Glial Fibrillary Acidic Protein / metabolism
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Immunoblotting / methods
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Immunohistochemistry / methods
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Male
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Mesencephalon* / drug effects
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Mesencephalon* / embryology
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Mesencephalon* / metabolism
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Pregnancy
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RNA, Messenger / biosynthesis
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Rats
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Transforming Growth Factor beta*
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Antioxidants
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Bmp7 protein, rat
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins
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Glial Fibrillary Acidic Protein
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RNA, Messenger
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Transforming Growth Factor beta
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Erythropoietin
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Tyrosine 3-Monooxygenase
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Dopamine beta-Hydroxylase
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Ascorbic Acid
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Dopamine