Regular consumption of caffeine permanently modifies the molecular functioning of the cells of the hippocampus, the seat of memory in the brain. This translates into greater neuronal plasticity, which may facilitate learning and improve memory.
Many people drink coffee. Some do it for taste, and many for the stimulating properties of caffeine. Indeed, the latter increases alertness and concentration in the hours following its consumption. It also has an effect on memory: several epidemiological studies and experimental studies attest to a benefit in the event of Alzheimer’s disease. A phase 3 study was even launched in 2021, in Lille, to assess the effect of caffeine on cognitive functions patients with an early or moderate form of this neurodegenerative disease (CAFCA study). However, the underlying molecular mechanisms remained unknown. This is why the teams of David Blum, at the Lille neuroscience & cognition research center*, and Anne-Laurence Boutillier, at the Strasbourg Cognitive and Adaptive Neuroscience Laboratory**, decided to tackle this question by studying the effects of chronic caffeine consumption in mice. ” There has been a lot of work on this substance, but which most often focused on acute consumption, that is to say occasional, and not on chronic consumption as is usually observed. In addition, these works do not provide information on the molecular changes induced downstream, once caffeine is fixed on its receptors in the brain. The objective of our project was to understand all this “, they explain.
In the experimental mouse model, the researchers focused their work on theseahorse, a brain structure that is the main site of memory and is affected in Alzheimer’s disease. They daily administered to the animals, orally, a moderate dose of caffeine, roughly equivalent to three cups of coffee per day in humans. After two weeks on this diet, the researchers studied the cells of their hippocampus, without a priori. They analyzed the expression profile of their genes (transcriptomic analyses), the chemical modifications of proteins attached to their DNA which are likely to modify this expression (epigenetic analyses), or even the nature of the proteins and other molecules present in cells (proteomics and metabolomics). This work was carried out in resting animals and in others subjected to a learning task. The results obtained were compared with those observed in mice which had not received caffeine.
These results, very rich in descriptive terms, allow several observations. First of all, caffeine does indeed leave long-term molecular “traces” in the hippocampus, particularly on the epigenetic level. And these traces are not the same depending on the cell type. For example, certain metabolic pathways appear to be down-modulated in non-neuronal cells of the hippocampus (glial cells), while activity in other pathways is up in neurons. But the most interesting concerns the observations made in a learning situation.
” As expected during a learning task, transcriptional activity that reflects the level of gene expression increases in the hippocampus. This is normal since this structure is mobilized to memorize this task. But we find that this increase is much stronger in animals that consume caffeine regularly. Looking closer, metabolic pathways reduced by caffeine in glial cells when animals are resting are ultimately activated when learning occurs. And those activated in the neurons are even more strongly activated. These data suggest that caffeine acts as a facilitator of the hippocampal response to a memory task, through a concerted action at the level of neuronal and non-neuronal cells. concludes David Blum.
* unit 1172 Inserm/University of Lille/CHU of Lille
** UMR7364 CNRS/University of Strasbourg
Source : Isabel Paiva et al. Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription. J Clin Investonline edition of May 10, 2022.