Journal Article

MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice

von Schimmelmann, Melanie, Kjems, Jørgen, Plotkin, Joshua L., Tan, Chan Lek, Surmeier, D. James, Greengard, Paul, Mann, Silas, Schaefer, Anne, Feinberg, Philip, Handler, Annie, Venø, Morten T., O'Carroll, Dónal

2013

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animal behavior / Animals / Behavioral neuroscience / Biological and medical sciences / Brain / Corpus Striatum - cytology / Dendrites - physiology / Epilepsy / Epilepsy - metabolism / Fundamental and applied biological sciences. Psychology / Gene expression / Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy / Hyperactivity / Hyperkinesis - metabolism / MAP Kinase Signaling System / Medical sciences / Messenger RNA / Mice / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 3 - metabolism / Motor ability / Motor Activity / Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration / Nervous system (semeiology, syndromes) / Neurology / Neurons / Neurons - physiology / Parkinson disease / Parkinsonian Disorders - metabolism / Parkinsonian Disorders - physiopathology / Phosphorylation / Prosencephalon - cytology / Prosencephalon - physiology / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA-Induced Silencing Complex - metabolism / Rodents / Seizures / Up-Regulation / Vertebrates: nervous system and sense organs