Grafting Human T2 Sympathetic Ganglion Into 6-OHDA-Induced Hemiparkinsonian Nude Rats:Behavioral And Histochemical Studies

• Main Author: 吳美英
• Other Authors: 劉德模
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/22937036973701562195

碩士 === 國防醫學院 === 藥理學研究所 === 85 === 　　Parkinson's disease (PD) is a progressive neurodegenerative disorder, which involves destruction of nigrostrial dopaminergic pathway. Medical treatments using L-DOPA or other dopaminergic agonists often result in side effects and drug resistance. We and others previously found that transplantation of fetal nigral tissue to the parkinsonian rats restores DA functions. In this study, we investigate the functional recovery as determined by rotational behavior and anatomical restoration of tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD) as revealed by immunocytochemistry after xenografting of human second thoracic sympathetic ganglion (T2G.) Unilateral nigrostriatal deafferentation was performed by injection of 6-hydroxydopamine (6-OHDA) into left medial forebrain bundle of chloral hydrate anesthetized Sprague-Dawley rats and Fischer 344 nude rats. The effectiveness of lesioning was evaluated by measuring methamphetamine (MA) -induce rotation. Our data revealed that grafting human T2G partially reversed the MA-induced rotation by two weeks in the nude rats. The rotational behavior gradually returned to the pre-grafting level by three months. More importantly, this functional recovery was substantiated by the TH and GAD immunoreactivities. Similar to the behavioral response, two to four weeks after tansplantation, we found numerous TH positive neurons and fibers within the grafted striatum. Although we did not observe obvious TH positive cells six to nine weeks after grafting, we found a considerable TH positive cells six to nine weeks after grafting, we found a considerabe TH positive fiber sprouting in the grafting region. Three months after grafting, only a few TH ositive neurons and fibers was noted. Contrary to the human T2G grafting, both SCG grafting and T2 fiber grafting failed to improve the rotational behavior and to reveal any TH immunoreactivity. Fetal VM grafting resulted in amelioration the rotational behavior at three months out not two weeks after transplantation. Concomitantly, the profound TH positive cells and dense plexus of TH fibers in the grafting region is responsible for long term behavioral improvement. Meanwhile, the up- or down-regulation of GAD expression around the grafting region was modulated by the TH expression suggesting a functional interaction between the donor and host cells. Taken together, our data revealed that human T2G xenograft can survive in the hosts and partially reverse the rotational behavior.