Mitochondrial dysfunction has been demonstrated to have a central role in Parkinson Disease (PD) pathophysiology. Some studies have indicated that PD causes an impairment in mitochondrial bioenergetics; however, the effects of PD on brain-region specific bioenergetics was never investigated before. This study aimed to evaluate mitochondrial bioenergetics in different rat brain structures in an in vitro model of PD using 6-OHDA. Rat brain slices of hippocampus, striatum, and cortex were exposed to 6-OHDA (100 μM) for 1 h and mitochondrial bioenergetic parameters, peroxide production, lactate dehydrogenase (LDH) and citrate synthase (CS) activities were analyzed. Hippocampus slices exposed to 6-OHDA presented increased peroxide production but, no mitochondrial adaptive response against 6-OHDA damage. Cortex slices exposed to 6-OHDA presented increased oxygen flux related to oxidative phosphorylation and energetic pathways exchange demonstrated by the increase in LDH activity, suggesting a mitochondrial compensatory response. Striatum slices exposed to 6-OHDA presented a decrease of oxidative phosphorylation and decrease of oxygen flux related to ATP-synthase indicating an impairment in the respiratory chain. The co-incubation of 6-OHDA with n-acetylcysteine (NAC) abolished the effects of 6-OHDA on mitochondrial function in all brain regions tested, indicating that the increased reactive oxygen species (ROS) production is responsible for the alterations observed in mitochondrial bioenergetics. The present results indicate a brain-region specific response against 6-OHDA, providing new insights into brain mitochondrial bioenergetic function in PD. These findings may contribute to the development of future therapies with a target on energy metabolism.

线粒体功能障碍已被证明在帕金森氏病（PD）病理生理中具有重要作用。一些研究表明，PD会导致线粒体生物能学受损。然而，PD以前从未研究过对脑区域特定生物能的影响。这项研究旨在评估体外不同大鼠脑结构中的线粒体生物能学使用6-OHDA的PD模型。将大鼠海马，纹状体和皮质的脑片暴露于6-OHDA（100μM）1小时，并分析线粒体的生物能参数，过氧化物的产生，乳酸脱氢酶（LDH）和柠檬酸合酶（CS）的活性。暴露于6-OHDA的海马片显示出增加的过氧化物生成，但没有针对6-OHDA损伤的线粒体适应性反应。暴露于6-OHDA的皮质切片显示与氧化磷酸化和能量途径交换有关的氧气通量增加，这由LDH活性的增加所证实，表明线粒体的代偿性反应。暴露于6-OHDA的纹状体切片显示出氧化磷酸化的降低和与ATP合酶相关的氧气通量的降低，表明呼吸链受损。6-OHDA与正乙酰半胱氨酸（NAC）的共同孵育消除了6-OHDA对测试的所有大脑区域中线粒体功能的影响，这表明增加的活性氧（ROS）产生是线粒体中观察到的变化的原因生物能学。目前的结果表明，针对6-OHDA的脑区域特异性反应，为PD中的线粒体生物能功能提供了新见解。这些发现可能有助于以能量代谢为目标的未来疗法的发展。目前的结果表明，针对6-OHDA的脑区域特异性反应，为PD中的线粒体生物能功能提供了新见解。这些发现可能有助于以能量代谢为目标的未来疗法的发展。目前的结果表明，针对6-OHDA的脑区域特异性反应，为PD中的线粒体生物能功能提供了新见解。这些发现可能有助于以能量代谢为目标的未来疗法的发展。