Citation

Magistretti PJ. Nature 2020; ePub(ePub): ePub.

Copyright

(Copyright © 2020, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1038/d41586-020-01975-5

PMID

32641790

Abstract

There is a general consensus that higher brain functions, and so, ultimately, behaviour, are controlled by dynamic communication at the synapses that connect neurons. Decades of psychopharmacology studies have validated this view, because most psychoactive drugs seem to exert their effects on mood and behaviour by interfering with the function of chemicals called neurotransmitters at synapses. This mechanism is proposed to mediate behavioural responses to compounds called cannabinoids1, which are the active ingredient of marijuana. But writing in Nature, Jimenez-Blasco et al. report a different mechanism of action for the cannabinoid tetrahydrocannabinol (THC) that involves the metabolism of lactate molecules in non-neuronal cells called astrocytes. This discovery cautions against an oversimplistic view of the mechanisms that underlie behaviour.

The role of lactate in brain metabolism is well established. Organelles called mitochondria are the primary subcellular site for the production of energy-carrying ATP molecules. But some ATP is generated in the cytoplasm through a process called glycolysis — this pathway also produces lactate, along with the molecule pyruvate. Mitochondria, in turn, process pyruvate through two cascades of biochemical reactions: the tricarboxylic acid cycle and the oxidative phosphorylation (OXPHOS) chain. The OXPHOS chain consumes oxygen to produce more ATP, with molecules called reactive oxygen species ...

Language: en

Keywords

Metabolism; Neuroscience