Caffeine Might Lead to Enduring Brain Changes.

Caffeine is the most widely consumed psychoactiveA drug or other substance that affects how the brain works and causes changes in mood, awareness, thoughts, feelings, or behavior. substance in the world, used by about 80% of the population, via dietary intake from coffee, tea, and soda beverages. Its popularity derives from its ability to enhance overall well-being as well as some central nervous system-related functions. In particular, habitual caffeine consumption by humans is associated with a reduction in all-cause mortality and cognitive decline. Moreover, multiple studies have documented that caffeine can enhance memory, highlighting the possibility that this stimulant could modulate the excitability of the hippocampusHippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders., a region responsible for learning. In fact, there is already considerable evidence that caffeine not only enhances basal synaptic transmissionthe ability of your brain to send signals from one cell to another in hippocampal slicesAcute hippocampal slice preparations are most often obtained from the adult rodent brain, are intended to be used for experimentation the same day that they are prepared, and are typically used to study various properties of individual neurons. but also long-term potentiationthe strength of connections in your brain., a molecular process that critically underlies memory consolidation. Therefore, there is already evidence that caffeine can enhance the ability of your brain to send signals from one cell to another, and it can also help improve the strength of connections in your brain.

Studying the Long Term Effects of Caffeine.

However, most of the currently available information about how caffeine might affect memory formation has been obtained within the context of short-term expsoure to caffeine and is thus of limited relevance for habitual/chronic consumption. Caffeine has been shown to block the effects of adenosine, a brain chemical that makes you tired. In short, caffeine can keep you awake and the molecular mechanisms through which it elicits its long-term effects remain largely obscure. To address this, the authors used a combination of unbiased omics techniquesOmics techniques aim to measure the total composition of a specific biochemical group. to determine the impact of chronic caffeine consumption on the epigenomeWithin the complete set of DNA in a cell (genome), all of the modifications that regulate the activity (expression) of the genes is known as the epigenome. Because epigenetic changes help determine whether genes are turned on or off, they influence the production of proteins in cells., transcriptomeThe transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment., proteomeA proteome is a set of proteins produced in an organism, system, or biological context. We may refer to, for instance, the proteome of a species (for example, Homo sapiens) or an organ (for example, the liver). The proteome is not constant; it differs from cell to cell and changes over time., and metabolomeMetabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome. of the mouse hippocampus.

Caffeine Has Positive Long-Term Effects.

The authors of this study observed that long-term (daily use for a long time) caffeine intake reduced the amount of lipids in cells (which are fats), mitochondria, and translation in murine bulk hippocampus tissue, some of which were identified at the different molecular levels analyzed, i.e. epigenome, transcriptome, proteome, and metabolome. In sharp contrast to what was observed within the context of bulk hippocampus tissue analysis, when they looked at the hippocampus in general, they found that caffeine did not affect the genes that were related to brain development. But when they looked at just the neurons, they saw that caffeine caused changes in the expression (activity) of certain genes. It had a special effect on genes that are related to memory and learning. Interestingly, these observations were corroborated by data showing that caffeine treatment not only induced an increase in glutamatergic synapse proteinsSynapses are important structures that connect neurons in the nervous system through chemical or electrical signals. Glutamatergic synapses are the main excitatory synapses in the brain. in the hippocampus but also significantly enhanced experience-driven transcriptional activitygenes activated by specific experiences in that region. In conclusion, caffeine not only caused an increase in the number of connections between nerve cells, it also caused those connections to work better.

Further Implication of Long-Term Coffee Intake.

Using many different kinds of scientific experiments, the authors figured out how changes in the genome (epigenome), RNA (transcriptome), proteins (proteome), and chemicals (metabolome) affect the brain's ability to learn after caffeine consumption. Altogether, their findings suggest that People who drink coffee on a regular basis (as oppose to people who don't) are better at encoding new information, and are better at learning, in part because their bodies are more capable of turning nutrients into energy. Of note, this study highlights the need to further study the molecular impact of caffeine in the homeostatic brainThe brain maintains the body's well-being. A constant conversation between the brain and the rest of the body takes place to keep physical conditions steady and balanced—a state called homeostasis., particularly regarding the differential mechanisms operating at the cellular level that modulate resting and active physiological brain activity. Additionally, their data could have far-reaching implications for the study of diseases characterized by synaptic dysregulationDysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders, and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia., such as Alzheimer’s disease. While caffeine exhibits normalizing properties in models of such disorders, the exact cell-specific molecular mechanisms remain to be uncovered. Finally, their data could also provide significant insights into how caffeine affects synapse formation within the context of brain development.

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Authors: Isabel Paiva, Lucrezia Cellai, Céline Meriaux, Lauranne Poncelet, Ouada Nebie, Jean-Michel Saliou, Anne-Sophie Lacoste, Anthony Papegaey, Hervé Drobecq, Stéphanie Le Gras, Marion Schneider, Enas M Malik, Christa E Müller, Emilie Faivre, Kevin Carvalho, Victoria Gomez-Murcia, Didier Vieau, Bryan Thiroux, Sabiha Eddarkaoui, Thibaud Lebouvier, Estelle Schueller, Laura Tzeplaeff, Iris Grgurina, Jonathan Seguin, Jonathan Stauber, Luisa V Lopes, Luc Buée, Valérie Buée-Scherrer, Rodrigo A Cunha, Rima Ait-Belkacem, Nicolas Sergeant, Jean-Sébastien Annicotte, Anne-Laurence Boutillier, David Blum


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