MPTP公司
神经毒素
多巴胺能
多巴胺
酪氨酸羟化酶
化学
内科学
内分泌学
生理盐水
药理学
生物
医学
作者
Andreas Leng,Anna Mura,Bastian Hengerer,Joram Feldon,Boris Ferger
标识
DOI:10.1016/j.bbr.2004.03.004
摘要
In Parkinson’s disease (PD) compensatory mechanisms such as an increase of the de novo biosynthesis of dopamine (DA) are thought to delay the onset of motor impairment. Here, we investigated whether the tyrosine hydroxylase (TH) inhibitor alpha-methyl-para-tyrosine (AMPT) affects behavioral deficits in the running wheel activity induced by the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immediately after MPTP treatment C57bl/6 mice showed reduced running wheel activity which lasted during the entire active phase (20:00 to 08:00 h), recovered to baseline levels in the following 2 days and remained stable up to the end of the experiment. AMPT challenge significantly reduced wheel running activity in MPTP-treated mice in the first 3 h after treatment. Post mortem HPLC analysis detected mean striatal DA levels in saline+saline and saline+AMPT-treated mice of 14.32 and 9.83 ng/mg, respectively and in MPTP+saline and MPTP+AMPT-treated mice of 1.73 and 0.69 ng/mg, respectively. Taken together, de novo biosynthesis of DA is a crucial component of the compensatory mechanisms which contributes to masking long-term behavioral deficits in the MPTP mouse model. Additionally, wheel running activity might provide a useful tool to study MPTP-induced behavioral deficits, shifts in circadian rhythmicity, and further compensatory mechanisms relevant to PD.
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