Adenosine receptor antagonists including caffeine alter fetal brain development in mice

Carla G. Silva, Christine Métin, Walid Fazeli, Nuno J. Machado, Sanja Darmopil, Pierre Serge Launay, Antoine Ghestem, Marie Pascale Nesa, Emilie Bassot, Eszter Szabó, Younis Baqi, Christa E. Müller, Angelo R. Tomé, Anton Ivanov, Dirk Isbrandt, Yuri Zilberter, Rodrigo A. Cunha, Monique Esclapez, Christophe Bernard

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Abstract

Consumption of certain substances during pregnancy can interfere with brain development, leading to deleterious long-term neurological and cognitive impairments in offspring. To test whether modulators of adenosine receptors affect neural development, we exposed mouse dams to a subtype-selective adenosine type 2A receptor (A2AR) antagonist or to caffeine, a naturally occurring adenosine receptor antagonist, during pregnancy and lactation. We observed delayedmigration and insertion of γ-aminobutyric acid (GABA) neurons into the hippocampal circuitry during the first postnatal week in offspring of dams treated with the A2AR antagonist or caffeine. This was associated with increased neuronal network excitability and increased susceptibility to seizures in response to a seizure-inducing agent. Adult offspring of mouse dams exposed to A2AR antagonists during pregnancy and lactation displayed loss of hippocampal GABA neurons and some cognitive deficits. These results demonstrate that exposure to A2AR antagonists including caffeine during pregnancy and lactation in rodents may have adverse effects on the neural development of their offspring.

Original languageEnglish
Article number197ra104
JournalScience Translational Medicine
Volume5
Issue number197
DOIs
Publication statusPublished - Aug 7 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Silva, C. G., Métin, C., Fazeli, W., Machado, N. J., Darmopil, S., Launay, P. S., Ghestem, A., Nesa, M. P., Bassot, E., Szabó, E., Baqi, Y., Müller, C. E., Tomé, A. R., Ivanov, A., Isbrandt, D., Zilberter, Y., Cunha, R. A., Esclapez, M., & Bernard, C. (2013). Adenosine receptor antagonists including caffeine alter fetal brain development in mice. Science Translational Medicine, 5(197), [197ra104]. https://doi.org/10.1126/scitranslmed.3006258