Ethanol and caffeine consumption modulates the expression of miRNAs in the cerebellum and plasma of UChB rats.

AIMS: The present study aimed to verify changes in cerebellar and plasmatic expression of miRNAs after the chronic consumption of ethanol and caffeine in the UChB rat, an experimental model for alcoholism. MATERIAL AND METHODS: Male rats at 5 months of age, were divided into the following groups (n = 10/group): 1. Ethanol (UChB rats receiving 10% ethanol solution and water ad libitum); 2. Ethanol + caffeine (UChB rats receiving 10% ethanol solution + 3g/l caffeine and water ad libitum); 3. Control (rats receiving water ad libitum). The cerebellum and plasma of the animals were collected and processed by RT-PCR for the miRNAs-155-5p, -146a-5p, -126-3p, -132-3p, -339-5p. KEY FINDINGS: Ethanol and caffeine were capable of regulating the expression of miRNAs associated with the inflammatory process in the tissue and plasma of the UChB rats. Increased expression of the analyzed miRNAs-155-5p, -146a-5p, -126-3p, -132-3p was observed for the cerebellar tissue in the Ethanol group and reduced expression of them in the Ethanol + caffeine group. In plasma, caffeine significantly elevated the miR-126-3p and miR-132-3p levels and decreased miR-155-5p levels. Ethanol consumption increased miR-146a-5p expression and decreased miR-339-5p levels. In brief, altered plasmatic levels of the miRNAs did not reflect the miRNAs levels found in cerebellar tissue. SIGNIFICANCE: Considering the results herein, we concluded that ethanol predisposes to an inflammatory process while caffeine has a neuroprotective effect on the cerebellar tissue.

Serum miRNAs are differentially altered by ethanol and caffeine consumption in rats.

Alcoholism is a multifactorial disease with high risk for dependence determined by genetic background, environmental factors and neuroadaptations. The excessive consumption of this substance is related to psychiatric problems, epilepsy, cardiovascular disease, cirrhosis and cancers. Caffeine is one of the most popular psychostimulants currently consumed in the world. The combination of ethanol and caffeine ingested by consuming "energy drinks" is becoming increasingly popular among young people. We analyzed the effect of simultaneous consumption of ethanol and caffeine on the serum profile of miRNAs differentially expressed in the ethanol-drinking rat model (UChB strain). Adult rats were divided into three groups (n = 5 per group): UChB group (rats fed with 1 : 10 (v/v) ethanol ad libitum); UChB + caffeine group (rats fed with 1 : 10 (v/v) ethanol ad libitum + 3 g L-1 of caffeine); control group (rats drinking water used as the control for UChB). The treatment with caffeine occurred from day 95 to 150 days old, totalizing 55 days of ethanol + caffeine ingestion. The expressions of microRNAs (miR) -9-3p, -15b-5p, -16-5p, -21-5p, -200a-3p and -222-3p were detected by Real Time-PCR (RT-PCR). The expressions of miR-9-3p, -15b-5p, -16-5p and -222-3p were upregulated in the UChB group. Conversely, simultaneous ingestion of ethanol and caffeine significantly reversed these expressions to similar levels to control animals, thus emphasizing that caffeine had a protective effect in the presence of ethanol. In addition, miR-21-5p was downregulated with ethanol consumption whereas miR-222-3p was unchanged. Ethanol and caffeine consumption was capable of altering serum miRNAs, which are potential biomarkers for the systemic effects of these addictive substances.