Long-term functional alterations following prenatal GLP-1R activation
Devon L Graham1, Haley S Madkour1, Brenda L Noble1
1Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL 32306, United States of America.
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.
Insights
Glucagon-like peptide-1 receptor (GLP-1R) activation during pregnancy minimally impacted mothers but altered offspring weight and anxiety-like behaviors. This suggests a sex-specific developmental role for GLP-1R in stress response.
Area of Science:
- Pharmacology
- Neuroscience
- Developmental Biology
Background:
- Glucagon-like peptide-1 receptor (GLP-1R) agonists are increasingly used for conditions beyond type 2 diabetes and obesity.
- The impact of GLP-1R activation during pregnancy on maternal and offspring health remains largely unknown.
Purpose of the Study:
- To investigate the effects of GLP-1R activation during pregnancy on maternal and offspring outcomes.
- To explore potential developmental roles of GLP-1R modulation in offspring behavior and physiology.
Main Methods:
- Female C57Bl/6J mice were treated with the GLP-1R agonist Exendin-4 prior to and throughout gestation.
- Maternal care, offspring weight, and behavioral domains (reward, depression, activity, cognition, anxiety) were assessed.
Main Results:
- Exendin-4 treatment had minimal effects on dams, potentially enhancing maternal care.
- Offspring exposed to Exendin-4 showed increased preweaning weight and altered anxiety-like behaviors.
- Few significant changes were observed in offspring reward, depression, activity, or cognition.
Conclusions:
- Pregnancy GLP-1R activation may have a developmental role in the maternal stress response, potentially sex-specific.
- Further research is needed to understand the long-term implications of prenatal GLP-1R exposure.
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