Fundamental Study on objective diagnosis and therapy effect decision of the dementia by the molecular imaging.

分子影像对痴呆客观诊断及治疗效果判定的基础研究。

• 批准号: 13670925
• 负责人: MORI Hirofumi
• 金额: $ 2.11万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670925/
• 关键词: Dementia; Receptor; Transporter; Neurotransplantation; Radiopharmaceutical; SPECT

Parkinsonian rats were stereotaxically infused 6-OHDA into the unilateral mesostriatal dopamine pathway and measured apomorphine-induced rotational behavior. Controls were infused saline instead of neurotoxin. Animals were divided into transplantation(TP) and sham-operated(S) groups. Ipsilateral vagal nodosal ganglion was surgically removed horn die neck and stereotaxically transplanted as nerve fragments into the ipsilateral striatum 2 weeks after nerotoxin infusion Sequential brain sections underwent autoradiography of dopaminergic system 2 weeks after operation. Densities of dopamine D1,D2 receptors and dopamine transporter(DAT) were assessed by in-vitro autoradiography using[^3H]SCH23390,[^3H]YM-09151-2 and[^3H]GBR12935. Significant DAT decrease in striatum was shown in the model animals compared with controls(P<0.0001). D_2 receptor in the ipsilateral striatum increased significantly in transplanted animals compared with sham-operated animals(S/R-,0.97±0.08;TP/R-,1.08±0.08;p=0.039 … More and S/R+,1.06±0.06;TP/R+,1.19±0.16;p=0.023), whereas DAT and D_1 receptor showed no significant changes. Our results suggest that vagal autotransplantation induces upregulation of D_2 receptor in the ipsilateral striatum. Autotransplantation showed no significant effect on DAT, although DAT imaging is a sensitive test for dopaminergic damage. We need hurther study on dopaminergic system imaging after neural transplantation.We evaluated the potencies of radioiodimted(-)-o-iodovesamicol [(-)-oIV] as a selective vesicular acetylcholine tmnsporter(VAChT) mapping agen. (-)-[^<125>1] oIV exhibited significant accumulationin rat brain. The regional brain distribution of radioactivity was similar for both (-)-[^<125>1] oIV and [^3H]vesamicol. The accumulation of (-)-[^<125>1] oIV in the brain was significant reduced by post-administration of unlabeled vesamicol(0.5μmol/kg^<-1>) and(-)-[^<125>1] oIV μmol/kg-1] in the other hand, the post-administration of sigma ligands hardy affected the accumulation of (-)-[^<125>1] oIV in die brain. These studies showed that (-)-[^<125>1] oIV, as well as [^3H]vesamicol, bound to VAChT with high affinity in die rat brain. Funhemore, (-)-[^<125>1] oIV binding in the ipsilateral cortex to the lesion was significantly reduced by 17.0%, compared with that in the contralateral cortex in a unilateral NBM-lesioned rat. These results suggested that radioiodimted(-)-[^<125>1] oIV may potentially be useful for the diagnosis of cholinergic neurodegenerative disorders. Less

帕金森病大鼠通过立体定向将6-OHDA注入单侧中脑纹状体多巴胺通路，并测量阿朴吗啡诱导的旋转行为。对照组注射生理盐水，而不是神经毒素。动物分为移植组(TP)和假手术组(S)。神经毒素注射2周后，手术切除同侧迷走神经结节，立体定向移植至同侧纹状体内。术后2周，连续行脑切片多巴胺能系统放射自显影。体外放射自显影测定多巴胺D_1、D_2受体和多巴胺转运体的密度。与对照组相比，模型组大鼠纹状体DAT显著降低(P&lt；0.0001)。与假手术animals(S/R-，0.97±0.08；TP/R-，1.08±0.08；p=0.039…相比，移植动物同侧纹状体D_2受体显著增加More和S/R+1.06±0.06；TP/R+1.19±0.16；P=0.023)，而DAT和D_1受体无明显变化。结果提示，迷走神经自体移植可诱导同侧纹状体D_2受体表达上调。自体移植对DAT没有显著影响，尽管DAT成像是多巴胺能损伤的敏感测试。我们对放射性碘标记的(-)-o-碘代氨基酚[(-)-OIV]作为一种选择性的囊泡性乙酰胆碱转运体(VAChT)标记剂的潜力进行了评价。(-)-[^&lt；125&gt；1]OIV在大鼠脑内显著蓄积。(-)-[125&gt；1]OIV和[~3H]Vesamicol在脑内的放射性分布相似。未标记的维沙米考(0.5Mol/kg)和(-)-[OIVμμ/kg-1]可显著减少(-)-OIV在脑内的蓄积；而Sigma配体HARDY后给药则影响脑内(-)-OIV的积聚。这些研究表明，(-)-[^&lt；125&gt；1]OIV和[^~3H]维沙米考与Vacht在大鼠脑内具有很高的亲和力。[Funhemore，(-)-[^&lt；125&gt；1]OIV结合量在单侧NBM损毁大鼠同侧皮质与病变部位的结合比对侧皮质显著降低17.0%。这些结果表明，放射性碘(-)-[125&gt；1]OIV可能对胆碱能神经退行性疾病的诊断有潜在的帮助。较少

项目成果

Shiba K.: "Chracterization of (-)radioisodinated (-)-ortho-iodovesamicol binding in rat brain preparations"Life Sciences. 71. 1591-1598 (2002)

Shiba K.：“大鼠脑制剂中 (-) 放射性碘化 (-)-邻碘维萨米考结合的表征”生命科学。

Shiba, K., Mori, H., Tonami, N.: "Evaluation of radioiodinated(-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter"Annals of Nuclear Medicine. 17・6. 451-456 (2003)

Shiba, K.、Mori, H.、Tonami, N.：“放射性碘化（-）-o-碘维沙考作为绘制囊泡乙酰胆碱转运蛋白的放射性示踪剂的评估”核医学年鉴 17・6（2003 年）。 ）

Shiba, K, Mori, H., et al.: "Chracterization of (-)radioisodinated (-)-ortho-iodovesamicol binding in rat braid preparations"Life Sciences. 71. 1591-1598 (2002)

Shiba, K, Mori, H. 等人：“大鼠辫状制剂中 (-) 放射性碘化 (-)-邻碘维沙考结合的表征”生命科学。

Shiba, K, Mori, H., et al.: "Evaluation of radioiodinated(-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter"Annals of Nuclear Medicine. 17・6. 451-456 (2003)

Shiba, K, Mori, H., et al.：“放射性碘化（-）-o-碘维沙考作为绘制囊泡乙酰胆碱转运蛋白的放射性示踪剂的评估”《核医学年鉴》17・6（2003）。

Shiba K.: "Evaluation of radioiodinated(-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter"Annals of Nuclear Medicine. 17(6). 451-456 (2003)

Shiba K.：“评估放射性碘化（-）-o-碘维萨米考作为放射性示踪剂用于绘制囊泡乙酰胆碱转运蛋白”核医学年鉴。