Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL 32306, United States of America.
Department of Psychology, Florida State University, Tallahassee, FL 32306, United States of America.
Neurotoxicol Teratol. 2021 Sep-Oct;87:106984. doi: 10.1016/j.ntt.2021.106984. Epub 2021 Apr 20.
Evidence supporting the use of glucagon-like peptide-1 (GLP-1) analogues to pharmacologically treat disorders beyond type 2 diabetes and obesity is increasing. However, little is known about how activation of the GLP-1 receptor (GLP-1R) during pregnancy affects maternal and offspring outcomes. We treated female C57Bl/6 J mice prior to conception and throughout gestation with a long-lasting GLP-1R agonist, Exendin-4. While GLP-1R activation has significant effects on food and drug reward, depression, locomotor activity, and cognition in adults, we found few changes in these domains in exendin-4-exposed offspring. Repeated injections of Exendin-4 had minimal effects on the dams and may have enhanced maternal care. Offspring exposed to the drug weighed significantly more than their control counterparts during the preweaning period and demonstrated alterations in anxiety-like outcomes, which indicate a developmental role for GLP-1R modulation in the stress response that may be sex-specific.
越来越多的证据支持使用胰高血糖素样肽-1（GLP-1）类似物来治疗 2 型糖尿病和肥胖症以外的疾病。然而，人们对 GLP-1 受体（GLP-1R）在怀孕期间的激活如何影响母婴结局知之甚少。我们在受孕前和整个妊娠期用长效 GLP-1R 激动剂 Exendin-4 处理雌性 C57Bl/6J 小鼠。虽然 GLP-1R 激活对成年期的食物和药物奖励、抑郁、运动活动和认知有显著影响，但我们发现暴露于 Exendin-4 的后代在这些领域几乎没有变化。重复注射 Exendin-4 对母体几乎没有影响，反而可能增强了母性照顾。在断奶前，暴露于药物的后代比对照组的体重明显增加，并且表现出焦虑样结果的改变，这表明 GLP-1R 调节在应激反应中具有发育作用，可能具有性别特异性。
