Abstract
The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal-regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson's-like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Corpus Striatum / cytology
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Dendrites / physiology
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Epilepsy / metabolism
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Hyperkinesis / metabolism
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MAP Kinase Signaling System
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Motor Activity*
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Neurons / physiology*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Prosencephalon / cytology
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Prosencephalon / physiology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Induced Silencing Complex / metabolism
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Up-Regulation
Substances
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MicroRNAs
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Mirn128 microRNA, mouse
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RNA, Messenger
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RNA-Induced Silencing Complex
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3