PET Imaging of Serotonin Transporters With 4-[18F]-ADAM in a Parkinsonian Rat Model With Porcine Neural Xenografts

被引：8
作者：
Chiu, Chuang-Hsin [1 ,2 ]
Li, I-Hsun [3 ,4 ]
Weng, Shao-Ju [5 ]
Huang, Yuahn-Sieh [5 ]
Wu, Shinn-Chih [6 ]
Chou, Ta-Kai [2 ]
Huang, Wen-Sheng [7 ,8 ]
Liao, Mei-Hsiu [9 ]
Shiue, Chyng-Yann [2 ]
Cheng, Cheng-Yi [1 ,2 ]
Ma, Kuo-Hsing [1 ,5 ]
机构：
[1] Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
[2] Triserv Gen Hosp, Natl Def Med Ctr, Dept Nucl Med, 325,Sec 2,Chenggong Rd, Taipei 114, Taiwan
[3] Triserv Gen Hosp, Natl Def Med Ctr, Dept Pharm Practice, Taipei, Taiwan
[4] Natl Def Med Ctr, Sch Pharm, Taipei, Taiwan
[5] Natl Def Med Ctr, Dept Biol & Anat, 161,Sec 6,Min Chuan E Rd, Taipei 114, Taiwan
[6] Natl Taiwan Univ, Dept Anim Sci & Technol, Taipei 10764, Taiwan
[7] Changhua Christian Hosp, Dept Nucl Med, Changhua, Taiwan
[8] Changhua Christian Hosp, Dept Med Res, Changhua, Taiwan
[9] Inst Nucl Energy Res, Taoyaun, Taiwan
来源：
CELL TRANSPLANTATION | 2016年 / 25卷 / 02期
关键词：
Parkinson's disease (PD); Rat model; Xenograft; Serotonin transporter; 4-[F-18]-ADAM; GRAFT-INDUCED DYSKINESIA; POSITRON-EMISSION-TOMOGRAPHY; NIGROSTRIATAL PATHWAY; 6-HYDROXYDOPAMINE LESIONS; VENTRAL MESENCEPHALON; CELL TRANSPLANTATION; FUNCTIONAL RECOVERY; IMMUNE-RESPONSES; LANYU PIG; DOPAMINE;
D O I：
10.3727/096368915X688236
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the nigrostriatal pathway. Apart from effective strategies to halt the underlying neuronal degeneration, cell replacement now offers novel prospects for PD therapy. Porcine embryonic neural tissue has been considered an alternative source to human fetal grafts in neurodegenerative disorders because its use avoids major practical and ethical issues. This study was undertaken to evaluate the effects of embryonic day 27 (E27) porcine mesencephalic tissue transplantation in a PD rat model using animal positron emission tomography (PET) coupled with 4-[F-18]-ADAM, a serotonin transporter (SERT) imaging agent. The parkinsonian rat was induced by injecting 6-hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal pathway. The apomorphine-induced rotation behavioral test and 4-[F-18]-ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the second week following 6-OHDA lesioning, the parkinsonian rat rotates substantially on apomorphine-induced contralateral turning. In addition, the mean striatal-specific uptake ratio (SUR) of 4-[F-18]-ADAM decreased by 44%. After transplantation, the number of drug-induced rotations decreased markedly, and the mean SUR of 4-[F-18]-ADAM and the level of SERT immunoreactivity (SERT-ir) in striatum were partially restored. The mean SUR level was restored to 71% compared to that for the contra lateral intact side, which together with the abundant survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery at the fourth week postgraft. In regard to the extent of donor-derived cells, we found the neurons of the xenografts from E27 transgenic pigs harboring red fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted area. Thus, transplanted E27 porcine mesencephalic tissue may restore dopaminergic and serotonergic systems in the parkinsonian rat. The 4-[F-18]-ADAM/animal PET can be used to detect serotonergic neuron loss in PD and monitor the efficacy of therapy.
引用
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页码：301 / 311
页数：11
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