Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.

Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
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DOI:
10.1016/j.molmet.2014.03.007
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发表时间:
2014-07
影响因子:
8.1
通讯作者:
Marsicano G
Marsicano G
中科院分区:
医学1区
文献类型:
--
作者:
Hebert-Chatelain E;Reguero L;Puente N;Lutz B;Chaouloff F;Rossignol R;Piazza PV;Benard G;Grandes P;Marsicano G

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脑线粒体活动主要参与能量平衡的中央控制。然而,当研究脑中的线粒体功能时,可能会得到不一致的结果,这取决于实验方法。例如,细胞器的免疫染色实验和生物化学分离使研究人员面临假阳性和/或假阴性结果的风险。例如,最近报道了大麻素1型(CB 1)受体在脑线粒体膜(mtCB 1)上的功能存在,并迅速受到挑战,声称最初的观察结果可能是由于人为结果。在这里,我们通过直接比较两项研究中使用的程序来解决这个问题。我们的研究结果表明,使用适当的控制和定量允许检测与CB 1受体抗体的mtCB 1受体,并且,如果线粒体组分的富集和纯化,CB 1受体激动剂可靠地降低脑线粒体呼吸。这些数据进一步强调了适应实验程序来研究脑线粒体功能的重要性。
Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expose investigators to risks of false positive and/or false negative results. As an example, the functional presence of cannabinoid type 1 (CB1) receptors on brain mitochondrial membranes (mtCB1) was recently reported and rapidly challenged, claiming that the original observation was likely due to artifact results. Here, we addressed this issue by directly comparing the procedures used in the two studies. Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria. These data further underline the importance of adapted experimental procedures to study brain mitochondrial functions.
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