Aix Marseille Université, INS, 13005 Marseille, France.
Sci Transl Med. 2013 Aug 7;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 (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.
怀孕期间摄入某些物质会干扰大脑发育，导致后代出现长期的神经和认知损伤。为了测试腺苷受体调节剂是否会影响神经发育，我们在妊娠和哺乳期使母鼠接触选择性腺苷 A2A 受体（A2AR）拮抗剂或咖啡因，咖啡因是一种天然的腺苷受体拮抗剂。我们观察到，在接受 A2AR 拮抗剂或咖啡因处理的母鼠的后代中，出生后第一周 GABA 神经元向海马回路的迁移和插入出现延迟。这与神经元网络兴奋性增加以及对致痫剂引起的癫痫发作的易感性增加有关。在妊娠和哺乳期暴露于 A2AR 拮抗剂的母鼠的成年后代表现出海马 GABA 神经元丢失和一些认知缺陷。这些结果表明，在妊娠和哺乳期期间，包括咖啡因在内的 A2AR 拮抗剂在啮齿动物中可能对其后代的神经发育产生不良影响。
