Abstract
BackgroundCaffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date.ResultsIn the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF). In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats.ConclusionThe results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.
Highlights
Caffeine is the most commonly consumed psycho-stimulant in the world
We noted a significant increase in the expression of Na+, K+-ATPase (204.2 ± 11.8% of control, P < 0.01) but not aquaporin 1 (AQP1) or carbonic anhydrase II (CAII) in the choroid epithelial cells of the caffeine-treated rats compared to the control rats (Figure 4A-C)
Because the "effect inversion" of caffeine might be caused by up-regulation of a receptor, we examined the expression of the adenosine receptors A1 and A2A, which have been identified as major targets of caffeine in the brain after chronic treatment with caffeine
Summary
Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; its effect on the structure of the brain has not been investigated to date. Methylxanthine caffeine is present in many common beverages, and is widely consumed worldwide [1,4]. Caffeine consumption has been estimated to be 76 mg per person per day worldwide, as high as 238 mg per person per day in the United States and Canada, and more than 400 mg per person per day in Sweden and Finland [5,6]. Caffeine is absorbed rapidly after oral administration and distrib-. Caffeine is metabolized to dimethyl- and monomethylxanthines, dimethyl and monomethyl uric acids, trimethyl- and dimethylallantoin, and uracil derivatives. The halflife of caffeine is ~5 hours in humans and ~1 hour in rats [4,7]
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