新生血管の構築による新たな統合失調症治療法の開拓に向けた実験的研究

旨在通过构建新血管开发新的精神分裂症治疗方法的实验研究

• 批准号: 20659179
• 负责人: 森 則夫
• 金额: $ 2.05万
• 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 Challenging Exploratory Research
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20659179/
• 关键词: 統合失調症; 微小循環; X線照射モデル; CD34; 中枢神経系; 移植; 神経幹細胞; X線照射; 血液脳関門

統合失調症では,微小循環系に異常が生じている可能性がある(統合失調症の微小循環異常仮説)。一方,近年,血管新生のメカニズム解明が進み,心臓や脳の虚血病変に新たな血管を形成し,機能回復を図る試みが始まっている。特に注目されているのは,ヒトCD34(+)血液幹細胞(以下CD34陽性細胞と称する)による毛細血管網の形成である。本研究では,我々の開発したX線照射モデルを統合失調症モデルとして用いた。成熟SD系雄性ラットの側脳室と海馬歯状回を含む領域に15GyのX線を分割照射し,これをモデル群とした。理研バイオリソースセンターより購入したCD34陽性細胞を用いた。麻酔下で右外頚動脈内にポリエチレン・カテーテル先端を内頚動脈分岐部に置き、1.6Mマンニトール液(10ml/kg)を注入。右半球のBBB透過性を亢進させた5分後にCD34陽性細胞(2×105または1×106/200μl)をハミルトン・マイクロシリンジで大腿静脈内から注入。細胞投与から1周間後に,4%パラホルムアルデヒド液で灌流固定し,脳冠状断凍結切片を作成。以下の一次抗体を用いて免疫染色を行った:(1)抗ヒトCD34モノクローナル抗体(CD34陽性細胞の指標)(2)抗ヒトCD146モノクローナル抗体(移植細胞由来の血管内皮細胞の指標)(3)抗von Willebrand Factor抗体,抗VCAM抗体,抗Laminin抗体(血管新生の活性化の指標)(4)抗ラットIgG抗体,抗ラットIgM抗体(ラット血中分子に対するBBB開放の指標)各々の抗体とBectastein ABC Elite kitにより可視化。これらからマンにトールを用いて脳内にCD34陽性細胞を生着させうることを確認した。今後はさらに他の条件での移植法の確認と、生着による行動異常の改善を確認する必要がある。

Schizophrenia, microcirculatory abnormalities, and the possibility of schizophrenia (schizophrenia and microcirculatory abnormalities). For one thing, in recent years, angiogenesis has been improved, new blood vessels have been formed in heart disease, and functional recovery has begun. In particular, CD34 (+) blood stem cells (hereinafter CD34 + cells) are involved in the formation of capillary networks. This study is aimed at exploring the use of X-ray radiation in schizophrenia. Mature SD males were exposed to 15Gy of X-ray in the lateral compartment of the hippocampus, and the hippocampus was exposed to 15Gy of X-ray in the lateral compartment of the hippocampus. In the case of the CD34-positive cells, they were used in the study. Under anesthesia, 1.6 M of solution (10ml/kg) was injected into the right outer artery at the tip of the inner artery. Five minutes after BBB permeability was increased in the right hemisphere, CD34 positive cells (2×105 and 1×106/200μl) were injected intravenously into the thigh. One week after the cells were injected, 4% of the cells were perfused and fixed in the solution, and coronal sections were prepared. The following primary antibodies were used for immunostaining:(1) anti-CD34 antibody (CD34-positive cell marker)(2) anti-CD146 antibody (vascular endothelial cell marker of transplanted cell origin)(3) anti-von Willebrand Factor antibody, anti-VCAM antibody, anti-Laminin antibody (angiogenesis marker)(4) anti-IgG antibody, anti-IgM antibody (BBB marker of open BBB marker of blood molecules). CD-34 positive cells were identified in the cells. In the future, it is necessary to confirm the transplant method for other conditions and to confirm the improvement of abnormal behavior.

项目成果

Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats: reversal by fluoxetine.

• DOI: 10.1371/journal.pone.0009260
• 发表时间: 2010-02-17
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Suzuki K;Okada K;Wakuda T;Shinmura C;Kameno Y;Iwata K;Takahashi T;Suda S;Matsuzaki H;Iwata Y;Hashimoto K;Mori N
• 通讯作者: Mori N

An association study of monoamine oxidase A (MAOA) gene polymorphism in methamphetamine psychosis

• DOI: 10.1016/j.neulet.2009.02.048
• 发表时间: 2009-05-15
• 期刊: NEUROSCIENCE LETTERS
• 影响因子: 2.5
• 作者: Nakamura, Kazuhiko;Sekine, Yoshimoto;Mori, Norio
• 通讯作者: Mori, Norio

Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine induced hyperlocomotion in adulthood

围产期窒息减少齿状颗粒细胞并加剧甲基苯丙胺引起的成年期过度运动

• 发表时间: 2008
• 期刊: PLoS ONE 3
• 作者: Wakuda T;Matsuzaki H;Suzuki K;Iwata Y;Shinmura C;Suda S;et al.
• 通讯作者: et al.

Association Studies and Gene Expression Analyses of the DISC1-Interacting Molecules, Pericentrin 2 (PCNT2) and DISC1-Binding Zinc Finger Protein (DBZ), With Schizophrenia and With Bipolar Disorder

• DOI: 10.1002/ajmg.b.30926
• 发表时间: 2009-10-05
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Anitha, Ayyappan;Nakamura, Kazuhiko;Mori, Norio
• 通讯作者: Mori, Norio

Metabolite alterations in the hippocampus of high-functioning adult subjects withautism

高功能成人自闭症受试者海马代谢的改变

• 发表时间: 2010
• 期刊: Int J Neuropsychopharmacol.
• 作者: Suzuki K;Nishimura K;Sugihara G;Nakamura K;Tsuchiya KJ;Matsumoto K,Takebayashi K;Isoda H;Sakahara H;Sugiyama T;Tsujii M;Takei N;Mori N
• 通讯作者: Mori N