title: A causative link between inner ear defects and long-term striatal dysfunction.
abstract: There is a high prevalence of behavioral disorders that feature hyperactivity in individuals with severe inner ear dysfunction. What remains unknown is whether inner ear dysfunction can alter the brain to promote pathological behavior. Using molecular and behavioral assessments of mice that carry null or tissue-specific mutations of Slc12a2, we found that inner ear dysfunction causes motor hyperactivity by increasing in the nucleus accumbens the levels of phosphorylated adenosine 3',5'-monophosphate response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase (pERK), key mediators of neurotransmitter signaling and plasticity. Hyperactivity was remedied by local administration of the pERK inhibitor SL327. These findings reveal that a sensory impairment, such as inner ear dysfunction, can induce specific molecular changes in the brain that cause maladaptive behaviors, such as hyperactivity, that have been traditionally considered exclusively of cerebral origin.
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Antoine
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Arezzo
authors.forename: Jean M
authors.initials: JM
authors.lastname: Hébert
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D007758:Ear, Inner / Q000473:pathology / Q000503:physiopathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006948:Hyperkinesis / Q000235:genetics / Q000503:physiopathology*; D007759:Labyrinth Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D001523:Mental Disorders / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009714:Nucleus Accumbens / Q000503:physiopathology*; D009925:Organ of Corti / Q000473:pathology / Q000503:physiopathology; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics; D064506:Solute Carrier Family 12, Member 2
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C424127:SL 327; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D000607:Aminoacetonitrile; D048049:Extracellular Signal-Regulated MAP Kinases