Adenosine receptor antagonists including caffeine alter fetal brain development in mice
Open accessAbstract
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.
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- Authors
- 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.
- Affiliations
- Inserm (FR)
- University Medical Center Hamburg-Eppendorf (DE)
- Centro de Neurociências e Biologia Celular (PT)
- University of Bonn (DE)
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2013-08-07
- Volume
- 5
- Issue
- 197
- Pages
- 197ra104-197ra104
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2024853882
- Cited by
- 177
- References
- 76
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 23 · 2022: 17 · 2021: 17 · 2020: 16 · 2019: 18 · 2018: 17 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 10 · 2013: 4
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
- orbi.uliege.be
- Licence
- other-oa
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- adenosine A2A receptor antagonists, caffeine, fetal brain development, prenatal drug exposure, hippocampus, neuronal network excitability, seizure susceptibility, cognitive impairment, pregnancy and lactation, teratogenicity
- MeSH terms
- Aging, Animals, Animals, Newborn, Haplorhini, Brain, Caffeine, Cell Movement, Cognition Disorders, Disease Susceptibility, Female, Fetus, Glutamates, Hippocampus, Nerve Net, Pregnancy, Seizures, Telencephalon, Receptors, Adenosine A2, Green Fluorescent Proteins, Mice, Rats, Purinergic P1 Receptor Antagonists, GABAergic Neurons
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