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MicroRNA-128 governs neuronal excitability and motor behavior in mice.

TitleMicroRNA-128 governs neuronal excitability and motor behavior in mice.
Publication TypeJournal Article
Year of Publication2013
AuthorsTan CLek, Plotkin JL, Venø MT, von Schimmelmann M, Feinberg P, Mann S, Handler A, Kjems J, D Surmeier J, O'Carroll D, Greengard P, Schaefer A
JournalScience
Volume342
Issue6163
Pagination1254-8
Date Published2013 Dec 6
ISSN1095-9203
KeywordsAnimals, Corpus Striatum, Dendrites, Epilepsy, Hyperkinesis, MAP Kinase Signaling System, Mice, MicroRNAs, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Motor Activity, Neurons, Parkinsonian Disorders, Prosencephalon, RNA, Messenger, RNA-Induced Silencing Complex, Up-Regulation
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.

DOI10.1126/science.1244193
Alternate JournalScience
PubMed ID24311694
PubMed Central IDPMC3932786
Grant List1DP2MH100012-01 / DP / NCCDPHP CDC HHS / United States
DA025962 / DA / NIDA NIH HHS / United States
DA10044 / DA / NIDA NIH HHS / United States
DP2 MH100012 / MH / NIMH NIH HHS / United States
NS34696 / NS / NINDS NIH HHS / United States
P01 DA010044 / DA / NIDA NIH HHS / United States
P50 MH090963 / MH / NIMH NIH HHS / United States
P50MH090963 / MH / NIMH NIH HHS / United States
R01 NS034696 / NS / NINDS NIH HHS / United States
R03 DA025962 / DA / NIDA NIH HHS / United States
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