Kasahara Yoshiyuki, Arime Yosefu, Kubo Yumiko, Fukui Asami, Sora Ichiro
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2011 Nov;31(5-6):195-9.
Dopamine transporter knockout (DAT KO) mice exhibited hyperdopaminergic tone in the nucleus accumbens and striatum, whereas they showed normal levels of extracellular dopamine in the prefrontal cortex. DAT KO mice showed numerous behavioral alterations that can be linked to abnormal dopaminergic function, including hyperlocomotion, deficits of prepulse inhibition (1PI) and impairment of working memory. PPI deficits were also shown in schizophrenic patients and hyperlocomotion was observed in AD/HD patients; therefore DAT KO mice had face validity for these psychiatric disorders. Impairment of neuronal development such as brain volume loss and decrease in spine density was reported especially in the prefrontal cortex of schizophrenia and AD/HD patients. We therefore investigated the neuronal development of DAT KO mice. Our results indicated that DAT KO mice had deficits of neuronal development in the prefrontal cortex similar to schizophrenia and AD/HD patients at least in part. These findings suggest that DAT KO mice are one of the useful models to investigate the impairment of neuronal development observed in psychiatric disorders including schizophrenia and AD/HD.
多巴胺转运体基因敲除（DAT KO）小鼠伏隔核和纹状体中呈现多巴胺能张力亢进，而前额叶皮质细胞外多巴胺水平正常。DAT KO小鼠表现出许多与多巴胺能功能异常相关的行为改变，包括活动亢进、前脉冲抑制（PPI）缺陷和工作记忆受损。精神分裂症患者也存在PPI缺陷，注意缺陷多动障碍（AD/HD）患者有活动亢进现象；因此，DAT KO小鼠在这些精神疾病方面具有表面效度。据报道，尤其是精神分裂症和AD/HD患者的前额叶皮质存在神经元发育受损，如脑容量减少和树突棘密度降低。因此，我们研究了DAT KO小鼠的神经元发育情况。我们的结果表明，DAT KO小鼠前额叶皮质的神经元发育缺陷至少部分类似于精神分裂症和AD/HD患者。这些发现表明，DAT KO小鼠是研究包括精神分裂症和AD/HD在内的精神疾病中观察到的神经元发育受损的有用模型之一。
