Implications of neural stem cells for the pathogenesis of schizophrenia : A new target for schizophrenia research

1.一种基于神经干细胞功能障碍假说的精神分裂症动物模型：(1)雄性SD大鼠前脑照射6次，每次5Gy.12周后，脑室下区和海马齿状回颗粒下区神经干细胞(BrdU阳性细胞)减少。甲基苯丙胺(MAP)(2 mg/kg，ip)后，小鼠的运动活动明显增加。或MK-801(0.2 mg/kg ip)被观察到了。受辐射大鼠的声脉冲前抑制和社会行为明显降低。Morris水迷宫结果显示，模型组大鼠的空间工作记忆和参考记忆存在中度损害。(2)据报道，LIFR缺陷小鼠的成体神经干细胞数量减少。在LIFR基因敲除小鼠中，MAP诱导的运动活动显著增加。然而，MK-801或预脉冲抑制惊厥反应后的行为变化并未观察到…更加激动人心。(3)将胚胎神经前体细胞移植到照射后3个月的大鼠双侧脑室和齿状回。神经干细胞移植后4周，MAP诱导的多动反应无明显改善。2.精神分裂症的外周生物标志物：Reelin是一种分泌型蛋白水解酶，在神经发育和可塑性中起重要作用。在精神分裂症中，reelin表达的减少是最有力的分子发现之一。载脂蛋白E受体2(ApoER2)和极低密度脂蛋白受体(VLDLR)是Reelin受体。为了寻找精神分裂症的外周生物标志物，我们研究了药物未用药的精神分裂症、心境障碍患者和健康对照组外周血淋巴细胞ApoER2和VLDLR的mRNA水平。我们观察到，与对照组相比，精神分裂症患者的VLDLR基因水平显著降低，但心境障碍患者的VLDLR基因表达水平没有明显下降。只有心境障碍患者的ApoER2基因水平显著降低。较少

1.An animal model for schizophrenia based on hypothesis of neural stem cell dysfunction :(1)Male Sprague-Dawley rats were irradiated to the forebrain using 6 fractions of 5 Gy. After 12 weeks, neural stem cells (BrdU positive cells) were diminished in both subventricular zone and hippocampal dentate gyrus subgranular zone. A significant increase in locomotor activity after administration of methamphetamine (MAP) (2 mg/kg i.p.) or MK-801 (0.2 mg/kg i.p.) was observed. Acoustic prepulse inhibition and social behaviors of the irradiated rats were significantly decreased. Moderate impairments of spatial working memory and reference memory assessed by Morris water maze were found in the model rats. (2)It has been reported that LIFR-deficient mice revealed a reduction in the number of adult neural stem cells. Locomotor activity induced by MAP was significantly increased in the LIFR knockout mice. However, behavioral change after MK-801 or prepulse inhibition of startle responces was not obse … More rved. (3)We transplanted embryonic neural precursor cells (NPCs) into the bilateral ventricles and the dentate gyri of the irradiated rats at 3 months after irradiation. The MAP-induce hyperactivity was not ameliorated at 4 weeks after the NPCs transplantation.2.Peripheral biological markers for schizophrenia :Reelin is a secretory protease with major roles in neurodevelopment and plasticity. A reduction of reelin expression is one of the most robust molecular findings in schizophrenia. Apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR) are reelin receptors. In search for peripheral biological markers for schizophrenia we have investigated mRNA levels of ApoER2 and VLDLR in peripheral blood lymphocytes of drug naive patients with schizophrenia, mood disorder and healthy controls. We observed a significant decrease of VLDLR mRNA levels in schizophrenia, but not those in mood disorder, compared with controls. A significant decrease in the ApoER2 mRNA level was found only in mood disorder. Less