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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / pharmacology
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Animals
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Animals, Newborn
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Apoptosis / drug effects
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Astrocytes / drug effects*
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Astrocytes / metabolism
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Behavior, Animal / drug effects
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Body Weight / drug effects
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Brain / cytology
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Brain / drug effects*
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Brain / growth & development
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Brain / metabolism
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Caffeine / administration & dosage
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Caffeine / pharmacology*
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Cell Differentiation / drug effects*
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Cell Proliferation / drug effects*
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Dose-Response Relationship, Drug
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Glial Fibrillary Acidic Protein / metabolism
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Immunohistochemistry
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Injections, Intraperitoneal
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Mice
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Microtubule-Associated Proteins / metabolism
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Models, Animal
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Nerve Growth Factors / metabolism
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Organ Size / drug effects
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Phenethylamines / pharmacology
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Pyrimidines / pharmacology
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Receptor, Adenosine A2A / drug effects
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Receptor, Adenosine A2A / metabolism
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S100 Calcium Binding Protein beta Subunit
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S100 Proteins / metabolism
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Synaptophysin / metabolism
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Time Factors
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Triazoles / pharmacology
Substances
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5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
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Glial Fibrillary Acidic Protein
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Microtubule-Associated Proteins
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Mtap2 protein, mouse
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Nerve Growth Factors
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Phenethylamines
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Pyrimidines
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Receptor, Adenosine A2A
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S100 Calcium Binding Protein beta Subunit
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S100 Proteins
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Synaptophysin
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Triazoles
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2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
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Caffeine
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Adenosine