TY - JOUR
T1 - A causative link between inner ear defects and long-term striatal dysfunction
AU - Antoine, Michelle W.
AU - Hübner, Christian A.
AU - Arezzo, Joseph C.
AU - Hébert, Jean M.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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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U2 - 10.1126/science.1240405
DO - 10.1126/science.1240405
M3 - Article
C2 - 24009395
AN - SCOPUS:84883485563
SN - 0036-8075
VL - 341
SP - 1120
EP - 1123
JO - Science
JF - Science
IS - 6150
ER -