Neuroprotective effects of (±)‐kavain in the MPTP mouse model of Parkinson's disease
Neuroprotective effects of (±)‐kavain in the MPTP mouse model of Parkinson's disease
复制标题
(±)-卡瓦因对帕金森病 MPTP 小鼠模型的神经保护作用
作者：
N. Schmidt;B. Ferger
这是第一个研究亲脂性kavapyrone（±）‐kavain在实验性MPTP（1‐甲基‐4‐苯基‐1,2,3,6‐四氢吡啶）帕金森病（PD）模型中的潜在保护作用的研究。雄性C57BL/6小鼠分别在单次给药MPTP （30 mg/kg s.c）前60分钟和后60分钟分别给予（±）- kavain（50、100或200 mg/kg i.p.）或vehicle。7 d后处死小鼠，用高效液相色谱电化学检测新纹状体多巴胺及其代谢物。此外，黑质切片进行酪氨酸羟化酶（TH）免疫细胞化学处理。为了确定（±）‐kavain （200 mg/kg）对MPTP代谢的影响，采用HPLC分析纹状体MPP+（1‐甲基‐4‐苯基吡啶）水平。单独MPTP治疗导致纹状体多巴胺水平显著下降，为生理盐水对照组的12.61%。低剂量（±）‐kavain（50和100 mg/kg）对MPTP诱导的多巴胺消耗仅显示不显著的衰减，但高剂量（±）‐kavain （200 mg/kg）显著拮抗多巴胺消耗，达到生理盐水对照组值的58.93%。值得注意的是，（±）kavain （200 mg/kg）完全阻止了MPTP诱导的TH免疫反应性下降和黑神经细胞的损失。纹状体MPP+水平未因（±）‐kavain处理而改变。总之，我们发现MPTP代谢不受（±）‐kavain的影响，并推测（±）‐kavain的抗谷氨酸能作用是其对MPTP毒性的保护作用。（±）‐Kavain可能是PD和其他谷氨酸能过度活动疾病动物模型进一步临床前研究的新候选药物。突触40:47-54 2001。©2001 Wiley‐Liss, Inc。
This is the first study to investigate the potential protective effects of the lipophilic kavapyrone (±)‐kavain in the experimental MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (±)‐kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLC with electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (±)‐kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP+ (1‐methyl‐4‐phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (±)‐kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP‐induced dopamine depletion, but a high dosage of (±)‐kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP‐induced decrease of TH‐immunoreactivity as well as the loss of nigral neurons was completely prevented by (±)‐kavain (200 mg/kg). Striatal MPP+ levels were not altered by (±)‐kavain treatment. In conclusion, we found that MPTP metabolism was not influenced by (±)‐kavain and postulate the antiglutamatergic effects of (±)‐kavain for its protective effects against MPTP toxicity. (±)‐Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity. Synapse 40:47–54, 2001. © 2001 Wiley‐Liss, Inc.
吗啡和乙基酮环佐辛挑战对大鼠脑电图和行为的不同长期影响。
影响因子：
5
作者：
Young,GA;Khazan,N
通讯作者：
Khazan,N