Murotani Tomotaka, Ishizuka Tomoko, Hattori Satoko, Hashimoto Ryota, Matsuzaki Shinsuke, Yamatodani Atsushi
Department of Medical Physics and Engineering, Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
Neurosci Lett. 2007 Jun 21;421(1):47-51. doi: 10.1016/j.neulet.2007.05.019. Epub 2007 May 22.
Schizophrenia is a chronic mental disorder and patients with this disease show positive and negative symptoms, cognitive dysfunction, and deficits in the processing of emotion. From previous studies, dopaminergic neurons are believed to be related to schizophrenic symptoms. Dysbindin (DTNBP1: dystrobrevin binding protein 1) gene is a susceptibility gene for schizophrenia, but the involvement of this gene in the dopaminergic tone remains unknown. In this paper, we studied regional contents of dopamine and its metabolite in the Sandy (Sdy) mouse which expresses no dysbindin protein. The brains of Sdy and wild-type (WT) mice were dissected into ten regions and dopamine (DA) and homovanillic acid (HVA) in each region were determined. DA contents were significantly lower in the cortex, hippocampus, and hypothalamus of Sdy mice than WT mice, while HVA contents showed no differences between the strains. Western blot analysis revealed there were no differences in the amount of tyrosine hydroxylase (TH) in the midbrain (MB) of both strains. The ratios of DA to HVA, which is an index of DA turnover, were higher in the cortex and the hippocampus, but not in the hypothalamus. These data demonstrate that DA turnover in the specific regions of the brain of the Sdy mouse was increased, and the Sdy mouse is a possible useful candidate animal for studying the pathogenic mechanism of schizophrenia.
精神分裂症是一种慢性精神障碍，患有这种疾病的患者会表现出阳性和阴性症状、认知功能障碍以及情绪处理缺陷。从先前的研究来看，多巴胺能神经元被认为与精神分裂症症状有关。失调结合蛋白（DTNBP1：肌萎缩蛋白结合蛋白1）基因是精神分裂症的一个易感基因，但该基因在多巴胺能张力中的作用仍不清楚。在本文中，我们研究了不表达失调结合蛋白的桑迪（Sdy）小鼠大脑中多巴胺及其代谢物的区域含量。将Sdy小鼠和野生型（WT）小鼠的大脑解剖成十个区域，并测定每个区域中的多巴胺（DA）和高香草酸（HVA）含量。Sdy小鼠大脑皮层、海马体和下丘脑的DA含量显著低于WT小鼠，而两品系之间的HVA含量没有差异。蛋白质免疫印迹分析显示，两品系中脑（MB）中酪氨酸羟化酶（TH）的含量没有差异。作为DA周转率指标的DA与HVA的比率在大脑皮层和海马体中较高，但在下丘脑中则不然。这些数据表明，Sdy小鼠大脑特定区域的DA周转率增加，并且Sdy小鼠可能是研究精神分裂症致病机制的有用候选动物。
