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Publication : A causative link between inner ear defects and long-term striatal dysfunction.

First Author  Antoine MW Year  2013
Journal  Science Volume  341
Issue  6150 Pages  1120-3
PubMed ID  24009395 Mgi Jnum  J:201156
Mgi Id  MGI:5511094 Doi  10.1126/science.1240405
Citation  Antoine MW, et al. (2013) A causative link between inner ear defects and long-term striatal dysfunction. Science 341(6150):1120-3
abstractText  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.
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