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

神经干细胞对精神分裂症发病机制的影响：精神分裂症研究的新目标

• 批准号: 15209036
• 负责人: MORI Norio
• 金额: $ 31.62万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209036/
• 关键词: schizophrenia; neural stem cell; animal model; LIFR knockout mice; VLDLR; ApoER2; x-irradiation; peripheral biological markers; 放射線; LIFR (leukemia inhibitory factor receptor); VLDLR (very low density lipoprotein receptor); ApoER2 (apolipoprote

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

1.基于神经干细胞功能障碍假说的精神分裂症动物模型的建立：（1）采用6次5戈伊剂量照射雄性SD大鼠前脑。12周后，脑室下区和海马齿状回颗粒下区的神经干细胞（BrdU阳性细胞）减少。在施用甲基苯丙胺（MAP）（2 mg/kg i. p.）或MK-801（0.2mg/kg i.p.）观察了辐射组大鼠的声前脉冲抑制和社会行为明显减少。Morris水迷宫检测结果显示，模型组大鼠的空间工作记忆和参考记忆均出现中度损害。(2)It据报道，LIFR缺陷小鼠显示成体神经干细胞数量减少。MAP诱导的自发活动在LIFR基因敲除小鼠中显著增加。然而，MK-801或惊吓反应的前脉冲抑制后的行为变化未观察到。 ...更多信息 服务。(3)We照射后3个月，将胚胎神经前体细胞（NPCs）移植到受照大鼠的双侧脑室和齿状回内。神经前体细胞移植4周后，MAP诱导的多动性无明显改善。2.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可靠的分子发现之一。载脂蛋白E受体2（ApoER 2）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学标志物，我们研究了精神分裂症、心境障碍和健康对照的药物初治患者外周血淋巴细胞中ApoER 2和VLDLR的mRNA水平。与对照组相比，我们观察到精神分裂症患者VLDLR mRNA水平显著降低，但心境障碍患者的VLDLR mRNA水平没有显著降低。ApoER 2 mRNA水平的显着下降，发现只有在情绪障碍。少

项目成果

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers

• DOI: 10.1001/archpsyc.63.1.90
• 发表时间: 2006-01-01
• 期刊: ARCHIVES OF GENERAL PSYCHIATRY
• 作者: Sekine, Y;Ouchi, Y;Mori, N
• 通讯作者: Mori, N

統合失調症の神経幹細胞機能異常仮説

精神分裂症的神经干细胞功能障碍假说

• 发表时间: 2005
• 期刊: 脳21 8・1
• 作者: Kato J;Kohyama T;Okazaki H;Desaki M;Nagase T;Rennard SI;Takizawa H.;森 則夫
• 通讯作者: 森 則夫

Association of FEZ1 gene-variants including Asp 123Glu with schizophrenia subset in Japan.

包括 Asp 123Glu 在内的 FEZ1 基因变异与日本精神分裂症亚群的关联。

• 发表时间: 2004
• 期刊: Biol Psychiatry 56
• 作者: Yamada K.#;Nakamura K.#;Minabe Y.# (#equally contributed to this work);Shigeno Y.;Takao H.;Toyota T.;Hattori E.;Takei N.;Sekine Y.;Suzuki K.;Iwata Y.;Miyoshi K.;Honda A.;Baba K.;Katayama T.;Tohyama M.;Mori N.;Yoshikawa T.
• 通讯作者: Yoshikawa T.

Effect of the acute and chronic administration of the putative atypical antipsychotic drug Y-931 (8-fluoro-12- (4-methylpiperazin-1-yl)-6H-[1]benzothieno[2,3b][1,5] benzodiazepine maleate) on spontaneously active rat midbrain dopamine neurons : an in vivo

假定的非典型抗精神病药物 Y-931（8-氟-12-（4-甲基哌嗪-1-基）-6H-[1]苯并噻吩[2,3b][1,5]苯二氮卓的急性和慢性给药效果

• 发表时间: 2004
• 期刊: Synapse. 51(1)
• 作者: Minabe Y;Hashimoto K;Shirayama Y;Ashby CR Jr.
• 通讯作者: Ashby CR Jr.

Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia

• DOI: 10.1016/j.biopsych.2005.08.016
• 发表时间: 2006-04-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Arai, M;Yamada, K;Itokawa, M
• 通讯作者: Itokawa, M