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

Research output: Contribution to journalArticle

67 Citations (Scopus)

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

Fingerprint

Purinergic P1 Receptor Antagonists
Fetal Development
Caffeine
Lactation
Brain
GABAergic Neurons
Pregnancy
Seizures
Aminobutyrates
Purinergic P1 Receptors
Rodentia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Silva, C. G., Métin, C., Fazeli, W., Machado, N. J., Darmopil, S., Launay, P. S., ... 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

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 journalArticle

Silva, CG, Métin, C, Fazeli, W, Machado, NJ, Darmopil, S, Launay, PS, Ghestem, A, Nesa, MP, Bassot, E, Szabó, E, Baqi, Y, Müller, CE, Tomé, AR, Ivanov, A, Isbrandt, D, Zilberter, Y, Cunha, RA, Esclapez, M & Bernard, C 2013, 'Adenosine receptor antagonists including caffeine alter fetal brain development in mice', Science Translational Medicine, vol. 5, no. 197, 197ra104. https://doi.org/10.1126/scitranslmed.3006258
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. / Adenosine receptor antagonists including caffeine alter fetal brain development in mice. In: Science Translational Medicine. 2013 ; Vol. 5, No. 197.
@article{ec393d0658074f46913a2da9fe0d9d14,
title = "Adenosine receptor antagonists including caffeine alter fetal brain development in mice",
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.",
author = "Silva, {Carla G.} and Christine M{\'e}tin and Walid Fazeli and Machado, {Nuno J.} and Sanja Darmopil and Launay, {Pierre Serge} and Antoine Ghestem and Nesa, {Marie Pascale} and Emilie Bassot and Eszter Szab{\'o} and Younis Baqi and M{\"u}ller, {Christa E.} and Tom{\'e}, {Angelo R.} and Anton Ivanov and Dirk Isbrandt and Yuri Zilberter and Cunha, {Rodrigo A.} and Monique Esclapez and Christophe Bernard",
year = "2013",
month = "8",
day = "7",
doi = "10.1126/scitranslmed.3006258",
language = "English",
volume = "5",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "197",

}

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 -