Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice

作者：Silva Carla G^*; Metin Christine; Fazeli Walid; Machado Nuno J; Darmopil Sanja; Launay Pierre Serge; Ghestem Antoine; Nesa Marie Pascale; Bassot Emilie; Szabo Eszter; Baqi Younis; Mueller Christa E; Tome Angelo R; Ivanov Anton; I**randt Dirk; Zilberter Yuri; Cunha Rodrigo A; Esclapez Monique; Bernard Christophe

来源：Science Translational Medicine, 2013, 5(197): 197ra104.

DOI：10.1126/scitranslmed.3006258

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 (A(2A)R) antagonist or to caffeine, a naturally occurring adenosine receptor antagonist, during pregnancy and lactation. We observed delayed migration and insertion of gamma-aminobutyric acid (GABA) neurons into the hippocampal circuitry during the first postnatal week in offspring of dams treated with the A(2A)R 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 A(2A)R antagonists during pregnancy and lactation displayed loss of hippocampal GABA neurons and some cognitive deficits. These results demonstrate that exposure to A(2A)R antagonists including caffeine during pregnancy and lactation in rodents may have adverse effects on the neural development of their offspring.

• 出版日期2013-8-7