CAFFEINE CONSUMPTION MODULATES THE EXPRESSION OF INFLAMMATORY MARKERS AND ADENOSINERGIC RECEPTORS IN CEREBELLUM OF UCHB RATS (VOLUNTARY ETHANOL CONSUMERS)

Introduction: The indiscriminate ethanol consumption is a risk factor to health, leading to inflammation in the Central Nervous System. Caffeine is one of the most consumed psychostimulant worldwide, present in drinks like coffee, green tea and a myriad of other foods. It acts through the adenosinergic system as a non-selective agonist of adenosinergic receptors. Adenosine is a key endogenous molecule that regulates tissue function by activating four G-protein-coupled adenosine receptors: A1, A2A, A2B, and A3. Cells of the immune system express these receptors and are responsive to the modulatory effects of adenosine in an inflammatory environment. The ethanol ingestion capable of influencing the expression of these receptors and it seems to be a pathway to create an inflammatory context in the nervous tissue. The cerebellum is one of the most affected components of the Central Nervous System due to ethanol consumption. Thus, caffeine has been thought of as a substance capable of antagonizing the harmful effects induced for ethanol once it has been documented as an anti-inflammatory bioactive compound in many systems. Objectives: To analyze the alterations of inflammatory markers and adenosinergic receptors in the cerebellum of rats submitted to the chronic consumption of ethanol and caffeine. Methods: Rats were divided into three groups (n=10/group): 1. UChB group (rats fed with 1:10 ethanol solution and water ad libitum); 2. UChB+caffeine group: (rats fed with 1:10 ethanol solution + caffeine 3g/L and water ad libitum); 3. Control group: Wistar (fed with water ad libitum). The cerebellar tissue was processed for Western Blotting and gene expressions analysis through RT-PCR for NFkB, TLR4, TLR2, MyD88, A1 e A2a. Results and discussion: The gene expression of the inflammatory markers was not altered after the ethanol or caffeine ingest but a significant difference was observed for the protein levels of the markers: NFkB, TLR4, and TLR2 were increased in UChB group indicating the establishment of an inflammatory context in the cerebellum. For these markers, caffeine was capable to modulate the levels of proteins comparable to Control group despite the ethanol consumption. The expression of the adenosinergic receptor A2a was not altered with the treatment for any group. However, gene expression of A1 was increased in UChB group, but its protein levels were found diminished for the same group. This fact indicates that adenosine levels are reduced following chronic ethanol exposure, which is associated with a reduced adenosinergic tone and contributes with the hypothesis of a post-transcriptional control about the elected markers. Conclusion: Ethanol led to an increase of inflammatory markers and caffeine had a neuroprotector action controlling the expression of the markers on a post-transcriptional level. Ethical approval and funding support: CEUA 4651-1/2017; FAPESP Process 2016/07410-8.
Key words: ethanol, caffeine, cerebellum