Adenosine receptor antagonists including caffeine alter fetal brain development in mice
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Adenosine receptor antagonists including caffeine alter fetal brain development in mice. / Silva, Carla G; Métin, Christine; Fazeli, Walid; Machado, Nuno J; Darmopil, Sanja; Launay, Pierre-Serge; Ghestem, Antoine; Nesa, Marie-Pascale; Bassot, Emilie; Szabó, Eszter; Baqi, Younis; Müller, Christa E; Tomé, Angelo R; Ivanov, Anton; Isbrandt, Dirk; Zilberter, Yuri; Cunha, Rodrigo A; Esclapez, Monique; Bernard, Christophe.
in: SCI TRANSL MED, Jahrgang 5, Nr. 197, 07.08.2013, S. 197ra104.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Adenosine receptor antagonists including caffeine alter fetal brain development in mice
AU - Silva, Carla G
AU - Métin, Christine
AU - Fazeli, Walid
AU - Machado, Nuno J
AU - Darmopil, Sanja
AU - Launay, Pierre-Serge
AU - Ghestem, Antoine
AU - Nesa, Marie-Pascale
AU - Bassot, Emilie
AU - Szabó, Eszter
AU - Baqi, Younis
AU - Müller, Christa E
AU - Tomé, Angelo R
AU - Ivanov, Anton
AU - Isbrandt, Dirk
AU - Zilberter, Yuri
AU - Cunha, Rodrigo A
AU - Esclapez, Monique
AU - Bernard, Christophe
PY - 2013/8/7
Y1 - 2013/8/7
N2 - 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 delayed migration 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.
AB - 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 delayed migration 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.
KW - Aging
KW - Animals
KW - Animals, Newborn
KW - Brain
KW - Caffeine
KW - Cell Movement
KW - Cognition Disorders
KW - Disease Susceptibility
KW - Female
KW - Fetus
KW - GABAergic Neurons
KW - Glutamates
KW - Green Fluorescent Proteins
KW - Haplorhini
KW - Hippocampus
KW - Mice
KW - Nerve Net
KW - Pregnancy
KW - Purinergic P1 Receptor Antagonists
KW - Rats
KW - Receptors, Adenosine A2
KW - Seizures
KW - Telencephalon
U2 - 10.1126/scitranslmed.3006258
DO - 10.1126/scitranslmed.3006258
M3 - SCORING: Journal article
C2 - 23926202
VL - 5
SP - 197ra104
JO - SCI TRANSL MED
JF - SCI TRANSL MED
SN - 1946-6234
IS - 197
ER -