Long-term functional alterations following prenatal GLP-1R activation

Neurotoxicol Teratol. 2021 Sep-Oct:87:106984. doi: 10.1016/j.ntt.2021.106984. Epub 2021 Apr 20.

Abstract

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.

Keywords: Anxiety; Brain; Development; Developmental programming; GLP-1; Pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cognition / drug effects
  • Exenatide / drug effects
  • Exenatide / metabolism*
  • Female
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide-1 Receptor / drug effects*
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Time*

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide 1
  • Exenatide