Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 43/b - 07100, Sassari, Italy.
Brain Res. 2013 Nov 13;1538:159-71. doi: 10.1016/j.brainres.2013.09.037. Epub 2013 Sep 27.
The neurotoxin MPTP is known to induce dopamine release and depletion of ATP in the striatum of rats. Therefore, we studied the changes induced by MPTP and pargyline protection both on striatal dopamine release and on extracellular energy metabolites in freely moving rats, using dual asymmetric-flow microdialysis. A dual microdialysis probe was inserted in the right striatum of rats. MPTP (25mg/kg, 15mg/kg, 10mg/kg) was intraperitoneally administered for three consecutive days. MAO-B inhibitor pargyline (15mg/kg) was systemically administered before neurotoxin administration. The first MPTP dose induced an increase in dialysate dopamine and a decrease of DOPAC levels in striatal dialysate. After the first neurotoxin administration, increases in striatal glucose, lactate, pyruvate, lactate/pyruvate (L/P) and lactate/glucose (L/G) ratios were observed. Subsequent MPTP administrations showed a progressive reduction of dopamine, glucose and pyruvate levels with a concomitant further increase in lactate levels and L/P and L/G ratios. At day 1, pargyline pre-treatment attenuated the MPTP-induced changes in all studied analytes. Starting from day 2, pargyline prevented the depletion of dopamine, glucose and pyruvate while reduced the increase of lactate, L/P ratio and L/G ratio. These in vivo results suggest a pargyline neuroprotection role against the MPTP-induced energetic impairment consequent to mitochondrial damage. This neuroprotective effect was confirmed by TH immunostaining of the substantia nigra.
神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）已知可诱导大鼠纹状体多巴胺的释放和三磷酸腺苷（ATP）的耗竭。因此，我们使用双不对称流动微透析技术，研究了 MPTP 诱导的变化以及对游离运动大鼠纹状体多巴胺释放和细胞外能量代谢物的影响，以及对游离运动大鼠纹状体多巴胺释放和细胞外能量代谢物的影响。将双微透析探针插入大鼠右侧纹状体。连续 3 天腹腔内给予 MPTP（25mg/kg、15mg/kg、10mg/kg）。MAO-B 抑制剂帕吉林（15mg/kg）在给予神经毒素前系统给予。第一剂 MPTP 引起纹状体透析液中多巴胺增加和二羟基苯乙酸（DOPAC）水平降低。首次神经毒素给药后，观察到纹状体葡萄糖、乳酸、丙酮酸、乳酸/丙酮酸（L/P）和乳酸/葡萄糖（L/G）比值增加。随后的 MPTP 给药显示多巴胺、葡萄糖和丙酮酸水平逐渐降低，同时乳酸水平和 L/P 和 L/G 比值进一步增加。在第 1 天，帕吉林预处理可减轻 MPTP 诱导的所有研究分析物的变化。从第 2 天开始，帕吉林可防止多巴胺、葡萄糖和丙酮酸的耗竭，同时降低乳酸、L/P 比值和 L/G 比值的增加。这些体内结果表明，帕吉林对线粒体损伤引起的 MPTP 诱导的能量损伤具有神经保护作用。该神经保护作用通过黑质的 TH 免疫染色得到证实。
