Transient Inhibition of Astrocytogenesis in Developing Mouse Brain Following Postnatal Caffeine Exposure

Abstract

Caffeine is frequently administered in human preterm newborns. Although some data suggest a potential risk for the developing brain, its impact has not been fully evaluated. We used a murine model of postnatal caffeine treatment in which mouse pups received intraperitoneal injections of caffeine from postnatal days 3 to 10. Caffeine exposure resulted in a transient reduction of glial fibrillary acidic protein and S100beta protein expression in various brain areas during the first 2 postnatal weeks (19.8% and 23.2% reduction in the hippocampus at P15, respectively). This effect was dose-dependent and at least partly involved a reduction of glial proliferation, as a caffeine-induced decrease of 5-bromodeoxyuridine incorporation was observed in the dentate gyrus and subventricular zone (25.8% and 26.6%, respectively) and no increase of programmed cell death (cleaved caspase-3 immunostaining) was observed at postnatal day 7. This effect could be reproduced with an antagonist of A(2a) adenosine receptor (A(2a)R) and was blocked by co-injection of an agonist. These results suggest that postnatal caffeine treatment might induce an alteration of astrocytogenesis via A(2a)R blockade during brain development. Although no obvious neuritic abnormalities (microtubule-associated protein 2 and synaptophysin immunostaining) were observed, postnatal caffeine treatment could have long-term consequences on brain function.