A Causative Link Between Inner Ear Defects and Long-Term Striatal Dysfunction
Michelle W. Antoine1, Christian A Hübner2, Joseph C. Arezzo1, Jean M. Hébert1,3,*
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.
2008年5月的爱思唯尔期刊《生物精神病学》（Biological Psychiatry）的一篇文章报道，γ-氨基丁酸中间神经元数量的减少增大了包括精神分裂症在内的各类精神疾病的患病风险。《生物精神病学》杂志的编辑、耶鲁大学医学院的John H. Krystal博士说：“该研究成果再次证明，基于动物实验的基础研究有助于发现治疗（甚至是预防）各类精神疾病的新分子靶区。”
