Ma Jeannine, Shaw Victoria E, Mitrofanis John
CNS Stability and Degeneration, Research School of Biological Sciences, Australian National University, Australia.
Parkinsonism Relat Disord. 2009 May;15(4):307-14. doi: 10.1016/j.parkreldis.2008.07.008. Epub 2008 Sep 14.
This study explores whether melatonin neuroprotects dopaminergic cells of the substantia nigra pars compacta (SNc) from degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (well-known animal model of Parkinson disease). BALB/c albino mice were divided into four experimental groups. In each, mice received three series (over a 24-h period) of two intraperitoneal injections (1h apart) in different combinations. The different groups and their combinations of injections were: (1) Saline (saline, saline); (2) Mel (melatonin, saline); (3) MPTP (saline, MPTP); (4) Mel-MPTP (melatonin, MPTP). Six days after the last injection, all mice were perfused transcardially with aldehyde fixative. Brains were processed for routine tyrosine hydroxylase (TH; rate limiting enzyme for dopamine production) immunochemistry and Nissl staining. Our results - using unbiased stereology - showed that there were more TH(+) (50%) and Nissl-stained (30%) cells in the SNc of the Mel-MPTP group compared to the MPTP group, indicating a clear saving or neuroprotection of these cells. In fact, we found no significant difference between the number of TH(+) and Nissl-stained SNc cells in the Mel-MPTP group compared to the controls, namely Saline and Mel groups. This indicated that melatonin pre-treatment potentially neuroprotected all the SNc cells from MPTP toxicity and death.
本研究探讨褪黑素是否能保护黑质致密部（SNc）的多巴胺能细胞免于在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠（帕金森病著名动物模型）中发生退化。将BALB/c白化小鼠分为四个实验组。每组小鼠在不同组合下接受三个系列（在24小时内）的两次腹腔注射（间隔1小时）。不同组及其注射组合如下：（1）生理盐水组（生理盐水，生理盐水）；（2）褪黑素组（褪黑素，生理盐水）；（3）MPTP组（生理盐水，MPTP）；（4）褪黑素-MPTP组（褪黑素，MPTP）。最后一次注射后六天，所有小鼠经心脏灌注醛类固定剂。对大脑进行常规酪氨酸羟化酶（TH；多巴胺生成的限速酶）免疫化学和尼氏染色处理。我们使用无偏倚立体学的结果表明，与MPTP组相比，褪黑素-MPTP组的SNc中TH(+)细胞（50%）和尼氏染色细胞（30%）更多，表明这些细胞明显得到挽救或神经保护。事实上，与对照组（即生理盐水组和褪黑素组）相比，我们发现褪黑素-MPTP组中TH(+)和尼氏染色的SNc细胞数量没有显著差异。这表明褪黑素预处理可能对所有SNc细胞起到神经保护作用，使其免受MPTP毒性和死亡影响。
