Jiao Yun, Dou Yuchen, Lockwood Georgina, Pani Amar, Jay Smeyne Richard
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biochemistry, University of Bath, Bath, UK.
J Parkinsons Dis. 2015;5(2):389-401. doi: 10.3233/JPD-140424.
MPTP and paraquat are two compounds that have been used to model Parkinson's disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal's core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal's death.
To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration.
In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP.
We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4-6 hours after MPTP.
The fatal hypothermic effects of MPTP can be abrogated through use of external heating.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和百草枯是两种已被用于在小鼠中模拟帕金森病的化合物。先前在两种非传统品系小鼠中的研究表明，单剂量的MPTP可引起体温变化，而百草枯的影响尚未得到研究。检查体温很重要，因为动物核心体温的微小波动会显著影响药物代谢，如果波动足够大甚至可能导致动物死亡。
确定外部加热如何改变C57BL/6J小鼠在给予MPTP后的存活率。
在本研究中，我们检查了MPTP（4×20毫克/千克，间隔2小时）和百草枯（2×10毫克/千克/周，共3周）对C57BL/6J小鼠核心体温的影响。还对接受MPTP治疗的小鼠进行了嘌呤和儿茶酚胺水平的相关性分析。
我们发现，MPTP可使C57BL/6J小鼠出现显著的体温过低，使其核心体温降至致命性体温过低的极限以下。与MPTP不同，百草枯未引起显著的体温过低。将动物放置在加热垫上可显著消除核心体温的下降。在加热和未加热条件下，接受MPTP治疗的小鼠在给药后2小时内纹状体和黑质中的三磷酸腺苷（ATP）均显著消耗，在MPTP给药结束后2小时开始恢复。MPTP给药后4-6小时起，纹状体多巴胺（DA）和3,4-二羟基苯乙酸（DOPAC）显著降低。
通过使用外部加热可消除MPTP的致命性体温过低效应。
