小柯机器人

法国波尔多大学Giovanni Marsicano和西班牙萨拉曼卡大学Juan P. Bolaños研究组合作取得新进展。他们发现葡萄糖代谢将星形胶质线粒体与大麻素作用联系起来。这一成果发表在2020年7月8日出版的《自然》杂志上。

他们显示与线粒体膜（mtCB1）相关的小鼠星形胶质1型大麻素受体的激活，阻碍了葡萄糖的代谢和大脑中乳酸的产生，从而导致神经元功能改变，进而削弱了社交互动中的行为反应。具体而言，星形胶质细胞mtCB1受体的激活降低了线粒体复合物I亚基NDUFS4的磷酸化，从而降低了复合物I的稳定性和活性，并通过低氧诱导因子1途径，导致星形胶质细胞中活性氧产生减少，最终导致神经元氧化还原应激和社交互动实验中的行为反应受损。这些效应中的每一种的遗传学和药理学校正，都消除了大麻素治疗对所观察到的行为的影响。这些发现表明，mtCB1受体信号传导可以直接调节星形胶质糖代谢，以微调小鼠的神经元活动和行为。

据了解，星状细胞从血液中吸收葡萄糖，为大脑提供能量，从而进行神经元活动和行为应答。相反，星形胶质细胞通过特定的神经递质受体受到神经元控制。然而，尚不清楚星形胶质受体的激活是否可以直接调节细胞葡萄糖代谢，以最终调节行为反应。

附：英文原文

Title: Glucose metabolism links astroglial mitochondria to cannabinoid effects

Author: Daniel Jimenez-Blasco, Arnau Busquets-Garcia, Etienne Hebert-Chatelain, Roman Serrat, Carlos Vicente-Gutierrez, Christina Ioannidou, Paula Gmez-Sotres, Irene Lopez-Fabuel, Monica Resch-Beusher, Eva Resel, Dorian Arnouil, Dave Saraswat, Marjorie Varilh, Astrid Cannich, Francisca Julio-Kalajzic, Itziar Bonilla-Del Ro, Angeles Almeida, Nagore Puente, Svein Achicallende, Maria-Luz Lopez-Rodriguez, Charlotte Joll, Nicole Dglon, Luc Pellerin, Charlne Josephine, Gilles Bonvento, Aude Panatier, Beat Lutz, Pier-Vincenzo Piazza, Manuel Guzmn, Luigi Bellocchio, Anne-Karine Bouzier-Sore, Pedro Grandes, Juan P. Bolaos, Giovanni Marsicano

Issue&Volume: 2020-07-08

Abstract: Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses1,2,3,4,5. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors5,6,7. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB1) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB1 receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB1 receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice.

DOI: 10.1038/s41586-020-2470-y

Source: https://www.nature.com/articles/s41586-020-2470-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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