The molecular effects of caffeine in the brain

The molecular effects of caffeine in the brain


Caffeine is the most widely used psychoactive substance in the world. While its effects on alertness and attention are widely known, the brain molecular mechanisms associated with its regular consumption have hitherto remained little known.

In mice, scientists have shown that regular caffeine consumption induces lasting molecular changes in the hippocampus, a structure that is essential for memory and degenerates into Alzheimer’s disease. The results obtained by different methods combining genomics, metabolomics and proteomics suggest that caffeine promotes the processing of information in this structure in response to a learning task, exerting a concerted action on neuronal and non-neuronal cells. Caffeine very significantly modifies the hippocampal epigenome in a differentiated way depending on whether it is neuronal or non-neuronal cells. This helps to promote the molecular processes associated with memory.

This study provides experimental evidence for a link between caffeine consumption and the neural processes involved in memory and provides a finer decipherment of the molecular effects of caffeine on different brain cells and a better understanding of the caffeine / memory link in the man. Notably, a potential beneficial effect in patients with Alzheimer’s disease is currently the subject of the CAFCA clinical trial (NCT04570085).

© I Paiva, AL Boutillier, D Blum, Biorender
Figure : Chronic Caffeine Mouse Treatment Induces Concerted Epigenetic Changes in Neural and Non-Neural Cells, Underlying Decreased Metabolism (Energy and Lipid) and Increased Genes and Proteins Involved in Neural Signaling and Plasticity . This is followed by fine-tuning of the metabolism and an increase in the ability of neurons to respond (priming) to a spatial learning task.

To find out more:
Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription.
Paiva I, Cellai L, Meriaux C, Poncelet L, Nebie O, Saliou JM, Lacoste AS, Papegaey A, Drobecq H, Le Gras S, Schneider M, Malik EM, Müller CE, Faivre E, Carvalho K, Gomez-Murcia V , Vieau D, Thiroux B, Eddarkaoui S, Lebouvier T, Schueller E, Tzeplaeff L, Grgurina I, Seguin J, Stauber J, Lopes LV, Buée L, Buée-Scherrer V, Cunha RA, Ait-Belkacem R, Sergeant N, Annicotte JS, Boutillier AL, Blum D
The Journal of Clinical Investigation May 10, 2022. https://doi.org/10.1172/JCI149371

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