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 language | English |
|---|---|
| Article number | 197ra104 |
| Journal | Science Translational Medicine |
| Volume | 5 |
| Issue number | 197 |
| DOIs | |
| Publication status | Published - Aug 7 2013 |
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ASJC Scopus subject areas
- Medicine(all)
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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: Science Translational Medicine, Vol. 5, No. 197, 197ra104, 07.08.2013.Research output: Contribution to journal › Article
}
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 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=84883887587&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883887587&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3006258
DO - 10.1126/scitranslmed.3006258
M3 - Article
C2 - 23926202
AN - SCOPUS:84883887587
VL - 5
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 197
M1 - 197ra104
ER -