Journal
SCIENCE
Volume 342, Issue 6163, Pages 1254-1258Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1244193
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Funding
- NIH [1DP2MH100012-01, DA025962, P50MH090963, DA10044, NS34696]
- Seaver Autism Foundation
- USAMRAA [W81XWH-090100402]
- JPB Foundation
- Lundbeck Foundation
- Center for Integrative Sequencing at Aarhus University
- CHDI Foundation
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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.
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