Fujita M, Shimada S, Tohyama M, Nishimura T
Division of Tracer Kinetics, Osaka University Medical School, Japan.
J Nucl Med. 1996 Jul;37(7):1214-8.
Dopamine (DA) has been considered to play an important role in the development of ischemic neuronal injury in the caudate putamen (CPu). The goal of this study was to examine the change in the dopamine transporter (DAT) after ischemic insult in CPu.
Male Mongolian gerbils (n = 10) were exposed to 10-min forebrain ischemia. Animals were decapitated 24 hr (n = 5) and 96 hr (n = 5) after ischemia. The change in the amount of DAT binding sites in CPu was evaluated by in vitro autoradiography with [125I]-beta-CIT (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester). In addition, the expression of DAT mRNA in CPu and the substantia nigra pars compacta (SNC) was examined.
Iodine-125-beta-CIT specific binding was significantly increased in dorsolateral CPu with ischemic damage both 24 hr and 96 hr after ischemia, with greater increase at 96 hr. DAT mRNA in SNC was also significantly increased 96 hr after ischemia, which corresponded with the increase of [125I] beta-CIT binding. However, DAT mRNA in SNC was decreased 24 hr after ischemia. In the ischemic lesion in CPu, no expression of DAT mRNA could be detected both 24 hr and 96 hr after ischemia.
The change in DAT after ischemic insult is clarified with [125I] beta-CIT. This increase of [125I] beta-CIT binding does not come from de novo expression of DAT in glial cells in the damaged area in CPu. This increase of beta-CIT binding reflects increase of DAT synthesis in DA neurons in SNC (96 hr) or other factors such as the impairment of the degradation of DAT in the damaged area in CPu.
多巴胺（DA）被认为在尾状核壳核（CPu）缺血性神经元损伤的发展中起重要作用。本研究的目的是检测CPu缺血损伤后多巴胺转运体（DAT）的变化。
雄性蒙古沙鼠（n = 10）接受10分钟的前脑缺血。在缺血后24小时（n = 5）和96小时（n = 5）将动物断头。用[125I]-β-CIT（3β-(4-碘苯基)托烷-2β-羧酸甲酯）通过体外放射自显影评估CPu中DAT结合位点数量的变化。此外，检测CPu和黑质致密部（SNC）中DAT mRNA的表达。
缺血后24小时和96小时，缺血损伤的背外侧CPu中碘-125-β-CIT特异性结合显著增加，96小时时增加更明显。缺血96小时后SNC中的DAT mRNA也显著增加，这与[125I]β-CIT结合的增加相对应。然而，缺血24小时后SNC中的DAT mRNA减少。在CPu的缺血损伤部位，缺血后24小时和96小时均未检测到DAT mRNA的表达。
用[125I]β-CIT阐明了缺血损伤后DAT的变化。[125I]β-CIT结合的这种增加并非来自CPu损伤区域神经胶质细胞中DAT的从头表达。β-CIT结合的这种增加反映了SNC中DA神经元中DAT合成的增加（96小时）或其他因素，如CPu损伤区域中DAT降解的受损。
