Abstract
Myelin, the insulating layers of membrane wrapped around axons by oligodendrocytes, is essential for normal impulse conduction. It forms during late stages of fetal development but continues into early adult life. Myelination correlates with cognitive development and can be regulated by impulse activity through unknown molecular mechanisms. Astrocytes do not form myelin, but these nonneuronal cells can promote myelination in ways that are not understood. Here, we identify a link between myelination, astrocytes, and electrical impulse activity in axons that is mediated by the cytokine leukemia inhibitory factor (LIF). These findings show that LIF is released by astrocytes in response to ATP liberated from axons firing action potentials, and LIF promotes myelination by mature oligodendrocytes. This activity-dependent mechanism promoting myelination could regulate myelination according to functional activity or environmental experience and may offer new approaches to treating demyelinating diseases.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Action Potentials / physiology
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Action Potentials / radiation effects
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Adenosine / pharmacology
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology
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Adenosine-5'-(N-ethylcarboxamide) / pharmacology
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Anesthetics, Local / pharmacology
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Animals
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Antibodies / pharmacology
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Astrocytes / physiology
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Astrocytes / radiation effects*
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Axons / drug effects
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Axons / metabolism
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Axons / radiation effects
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Azo Compounds
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Blotting, Western / methods
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Cell Communication / drug effects
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Cell Communication / physiology*
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Cell Communication / radiation effects
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Cell Count / methods
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Cells, Cultured
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Cerebral Cortex / cytology
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Coculture Techniques / methods
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DNA-Binding Proteins / metabolism
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Dose-Response Relationship, Drug
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Drosophila Proteins / metabolism
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Drug Interactions
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Electric Stimulation / methods*
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Embryo, Mammalian
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Enzyme-Linked Immunosorbent Assay / methods
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Ganglia, Spinal / cytology
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Gene Expression / drug effects
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Immunohistochemistry / methods
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Leukemia Inhibitory Factor
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Mice
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Models, Biological
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Myelin Basic Protein / metabolism
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Myelin Proteins / metabolism*
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Myelin-Associated Glycoprotein / metabolism
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Myelin-Oligodendrocyte Glycoprotein
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Naphthalenes
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology
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O Antigens / metabolism
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Oligodendroglia / physiology*
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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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Stem Cells
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Tetrodotoxin / pharmacology
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Thionucleotides / pharmacology
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Time Factors
Substances
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Anesthetics, Local
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Antibodies
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Azo Compounds
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Brd protein, Drosophila
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DNA-Binding Proteins
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Drosophila Proteins
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Interleukin-6
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Leukemia Inhibitory Factor
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Lif protein, mouse
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MOG protein, human
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Mog protein, mouse
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Mog protein, rat
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Myelin Basic Protein
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Myelin Proteins
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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Naphthalenes
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O Antigens
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RNA, Messenger
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Thionucleotides
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Adenosine-5'-(N-ethylcarboxamide)
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Tetrodotoxin
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Adenosine Triphosphate
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Sudan Black B
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Adenosine
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2-methylthio-ATP