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

1.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Sprague-Dawley大鼠以5 Gy的6次剂量照射前脑。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）均减少。在给予甲基苯丙胺（MAP） （2 mg/kg i.p.）或MK-801 （0.2 mg/kg i.p.）后，运动活动显著增加。受辐射大鼠的声脉冲前抑制和社会行为显著降低。Morris水迷宫评价模型大鼠空间工作记忆和参考记忆出现中度损伤。(2)据报道，lifr缺陷小鼠显示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或脉冲前抑制惊吓反应后的行为改变并不明显。(3)在照射后3个月，将胚胎神经前体细胞（NPCs）移植到大鼠双侧脑室和齿状回。移植后4周，map诱导的多动未见改善。精神分裂症的外周生物学标志物：Reelin是一种分泌性蛋白酶，在神经发育和可塑性中起重要作用。reelin表达的减少是精神分裂症中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）是卷曲蛋白受体。为了寻找精神分裂症的外周生物学标志物，我们研究了精神分裂症患者、情绪障碍患者和健康对照者外周血淋巴细胞中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 mRNA水平显著下降，但心境障碍患者的VLDLR mRNA水平没有显著下降。ApoER2 mRNA水平的显著下降仅在情绪障碍中发现。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