Fundamental Study on Assessment of Neurotransplantation Using Nuclear Medicine Imaging

利用核医学成像评估神经移植的基础研究

• 批准号: 08671011
• 负责人: MORI Hirofumi
• 金额: $ 1.22万
• 依托单位: KANAZAWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671011/
• 关键词: Alzheimer's disease; Lesion of Nucleus Basalis Magnocellularis; Acetylcholine; Receptor; Neurotransplantation; Transporter

Alzheimer's disease is one of most troublesome problems encountered in the elderly population. One proposed hypothesis is that a deficit in cholinergic neurotransmission in Alzheimer's disease underlies this serious symptom of the disease. Cholinergic denervation rat model by producing an unilateral lesion of nuleus basalis magnocellularis (NBM) are reported to a model of cognitive deficits, one of instructive models of Alzheimer's disease (AD). The neurotransplantation is now promising as an effective strategy for functional repair in a variety of neural systems in disorders such as Parkinson's disease. In this study autotransplantation of vagal ganglion was performed to NBM lesioned rats. The effects of cholinergic grafts on cholinergic systems evaluated by autoradiographic images in duration of 1,2 and 4 weeks after surgery. Cerebral blood flow (CBF), muscarinic acetylcholine receptor (mAChR), m1 and m2 subtype of AChR-mRNA images were obtained using 99mTc-hexamethyl-propyleneamine … More oxime (99mTc-HMPAO), [3H] quinuculidinal benzilate, 35S-labeled oligonucleotide probes by in situ hybridization respectively. Also acetylcholine transporter images were obtained using [3H] vesamicol and [3H] hemicholinium-3 (3H-HC-3). The autoradiograms were quantified by bio-imaging analyzer using imaging plate ; the regions of interesting (ROIs) were set in cortex of the affected side and unaffected side symmetrically, and the affected-side/unaffected-side ratios (AU ratio) were calculated from these mean photo-stimulated luminescence (PSL) rates. In both NBM lesioned and autoransplanted rats, there were no remarkable changes of the AU ratio at CBF,mAChR,m1mAChR-mRNA and m2mAChR-mRNA images. On the other hand, the [3H] vesamicol images of the NBM lesioned rats showed significant reduction of the mean AU ratio at 1,2 and weeks after lesioning (P<0.01). Furthermore, the mean AU ratio in autotransplanted rats gradually increased and significantly improved 4 weeks after transplantation (p<0.05). There were no remarkable changes of the AU ratio at 3H-HC-3. Clinically emission computed tomography (ECT) with radiolabeled vesamicol may be a potential procedure for the assessment of neurotransplantation therapy on patients with AD. Less

阿尔茨海默氏病是老年人遇到的最棘手的问题之一。一个被提出的假说是，阿尔茨海默病中胆碱能神经传递的缺陷是这种严重症状的基础。本文报道了通过损毁一侧基底大细胞核（NBM）建立的胆碱能神经损伤大鼠模型，该模型是阿尔茨海默病（AD）的指导性模型之一。神经移植是治疗帕金森病等多种神经系统疾病的有效方法。本研究采用自体迷走神经节移植术治疗NBM损伤大鼠。术后1、2、4周放射自显影评价胆碱能移植物对胆碱能系统的影响。用99 mTc-六甲基丙烯胺（99 mTc-hexamethyl-propyleneamine，99 mTc-HMP）对脑血流量（CBF）、毒蕈碱型乙酰胆碱受体（mAChR）、m1和m2亚型AChR-mRNA进行显像 ...更多信息 分别用~（99）mTc-HMPAO、~ 3 H-二苯甲酸奎宁酸酯、~（35）S标记的寡核苷酸探针进行原位杂交。还使用[3 H] vesamicol和[3 H] hemicholinium-3（3 H-HC-3）获得乙酰胆碱转运蛋白图像。用生物成像仪对放射自显影图进行定量分析，在患侧和健侧皮质对称设置感兴趣区（ROI），根据平均光刺激发光（PSL）率计算患侧/健侧比值（Au ratio）。在NBM损毁和自体移植的大鼠中，CBF、mAChR、m1 mAChR-mRNA和m2 mAChR-mRNA图像的Au比值均无明显变化。另一方面，NBM损伤大鼠的[3 H] vesamicol图像显示损伤后1、2和周的平均Au比值显著降低（P<0.01）。移植后4周，自体肾移植大鼠的平均Au比值逐渐升高，与移植前相比有显著性差异（p<0.05）。在3 H-HC-3下，Au比率无显著变化。放射性标记的vesamicol的临床发射计算机断层扫描（ECT）可能是一个潜在的程序，用于评估AD患者的神经移植治疗。少

项目成果

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