Transient inhibition of astrocytogenesis in developing mouse brain following postnatal caffeine exposure
Luc Desfrere1, Paul Olivier, Leslie Schwendimann
1Inserm, U676, 75019 Paris, France. luc.desfrere@cch.ap-hop-paris.fr
Insights
Postnatal caffeine administration in preterm newborns may alter brain development by reducing glial cell proliferation via adenosine receptor blockade. Further research is needed to understand potential long-term effects on brain function.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Caffeine is commonly given to preterm infants.
- Potential risks of caffeine to the developing brain require further investigation.
Purpose of the Study:
- To evaluate the impact of postnatal caffeine treatment on brain development in a murine model.
- To investigate the underlying mechanisms, including glial cell proliferation and adenosine receptor involvement.
Main Methods:
- Murine pups received daily intraperitoneal caffeine injections from postnatal days 3-10.
- Assessed expression of glial fibrillary acidic protein, S100beta, 5-bromodeoxyuridine incorporation, and cleaved caspase-3.
- Utilized A(2a) adenosine receptor antagonists and agonists to explore receptor involvement.
Main Results:
- Caffeine treatment transiently reduced glial protein expression and glial proliferation in a dose-dependent manner.
- A(2a) adenosine receptor blockade mimicked and was blocked by agonists, indicating receptor involvement.
- No significant neuritic abnormalities or increased cell death were observed.
Conclusions:
- Postnatal caffeine may alter astrocytogenesis through A(2a) adenosine receptor blockade during brain development.
- While immediate abnormalities were not evident, long-term consequences on brain function are possible.
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.
