Brain protection and recirculation therapy with non-viral vector gene

非病毒载体基因的脑保护和再循环治疗

• 批准号: 14370432
• 负责人: SAITOH Youichi
• 金额: $ 7.55万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370432/
• 关键词: gene therapy; HVJ-E; Tet-on system; NL1; Gene Therapy; Brain protection; HGF; Liposome; Gene therapy

1)To create a cell line with controlled and specific secretion of b-endorphin, a new fusion gene was constructed by joining human b-endorphin coding sequence to part of NL1 gene. HEK293 cells carrying Tet-on system transfected with this fusion gene secreted b-endorphin in a dose-dependent manner upon doxycycline(Dox) administration. This cell line was encapsulated and transplanted in the monkey's CSF space, but failed to respond the administered Dox (i.m.). On the other hand, Neuro2A-Tet-on-POMC cells were encapsulated and transplanted in the monkey's CSF space. They secreted ACTH in the monkey's CSF in a dose-dependent manner upon Dox administration. From these results, peptide secretion from encapsulated cells in the CSF space can be controlled through Tet-on system. HEK293 cells may not fit for this experiment.2)HVJ-E containing the lacZ, GFP-ODN or DsRed was injected into the cisterna magna of rats and monkeys, and they were perfused with 4% paraformaldehyde. Their brains and meninges were removed and 50-μm-thick sections were made. The brains and meninges of both monkeys and rats were examined about the gene transfection of lacZ, GFP-ODN or DsRed. The efficacy of gene transfection was not stable in both animals. It's reason wasnot clear and the physiological examination has not been done.

1)通过将人b-内啡肽编码序列与NL1基因的部分序列连接，构建了b-内啡肽分泌可控和特异分泌的细胞系。携带该融合基因Tet-on系统的HEK293细胞在多西环素(Dox)作用下以剂量依赖的方式分泌b-内啡肽。该细胞系被包裹并移植到猴子的脑脊液腔内，但对注射的Dox(肌肉注射)没有反应。另一方面，将Neuro2A-Tet-on-POMC细胞包裹并移植到猴的脑脊液间隙中。他们在猴子的脑脊液中分泌ACTH，并以剂量依赖的方式给药。根据这些结果，脑脊液间隙中被包裹的细胞的多肽分泌可以通过Tet-on系统进行控制。2)将含有LacZ、GFP-ODN或DsRed的HVJ-E注入大鼠和猴的枕大池，并用4%多聚甲醛灌流。取脑和脑膜，制作50μm厚的切片。检测LacZ、GFP-ODN和DsRed基因在猴和大鼠脑和脑膜中的表达情况。基因转染法在两种动物中的效果并不稳定。原因尚不清楚，生理检查也未做。

项目成果

An investigation into the role into the role of Bcl-2 in neuroendocrine differentiation.

Bcl-2 在神经内分泌分化中的作用的研究。

• 发表时间: 2005
• 期刊: Biochem Biophys Res Commun 326
• 作者: I.S.Cadden;et al.
• 通讯作者: et al.

Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and its induction in Alzheimer brains

Caspase-4参与内质网应激诱导的细胞凋亡及其在阿尔茨海默病脑中的诱导

• 发表时间: 2004
• 期刊: J CellBiol 165
• 作者: Hitomi J

前頭葉てんかんの1事例からみた症候学的メカニズム-合成開口脳磁図による解析-

从额叶癫痫病例看出症状机制 - 使用合成孔径脑磁图进行分析 -

• 发表时间: 2002
• 期刊: 臨床脳波 44
• 作者: Tomishima T;et al.;Saitoh Y;齋藤洋一;加藤天美
• 通讯作者: 加藤天美

コンピュータ支援画像誘導手術

计算机辅助图像引导手术

• 发表时间: 2002
• 期刊: 機能的脳神経外科の最先端 16
• 作者: Tomishima T;et al.;Saitoh Y;齋藤洋一;加藤天美;加藤天美
• 通讯作者: 加藤天美

Application of SAM virtual sensor method for localization of origins and propagation of epileptic discharges in refratory frontal lobe epilepsy

SAM虚拟传感器方法在难治性额叶癫痫癫痫放电起源和传播定位中的应用

• 发表时间: 2002
• 期刊: BIOMAG
• 作者: Kenji Tada;Kato A
• 通讯作者: Kato A