Journal article
Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction
Psychiatry research, Vol.337, 115951
07/2024
DOI: 10.1016/j.psychres.2024.115951
PMCID: PMC11267813
PMID: 38735240
Abstract
Highlights
•Adolescent isolation of rodents dually affects metabolism and mental well-being•Adolescent isolation changes gene transcription in neural 5-HT & GLP-1 circuits•5-HT neurons of isolated mice are resistant to the GLP-1R agonist semaglutide•Semaglutide rescues deficits in social interaction induced by this paradigm
Abstract
Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.
Graphical abstract
Mice were either singly housed (top left) or group housed (top right) throughout adolescence. In adolescent-isolation mice, this induced changes in neural gene expression (center) with deficits in social interaction (bottom left). Acute injection of the GLP-1 receptor agonist semaglutide was sufficient to rescue social interaction behavior (bottom).
Details
- Title: Subtitle
- Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction
- Creators
- Louis J. Kolling - University of IowaKanza Khan - Daemen CollegeRuixiang Wang - University of IowaSamantha R. Pierson - University of IowaBenjamin D. Hartman - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, USANagalakshmi Balasubramanian - University of IowaDeng-Fu Guo - University of IowaKamal Rahmouni - University of IowaCatherine A. Marcinkiewcz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Psychiatry research, Vol.337, 115951
- DOI
- 10.1016/j.psychres.2024.115951
- PMID
- 38735240
- PMCID
- PMC11267813
- NLM abbreviation
- Psychiatry Res
- ISSN
- 0165-1781
- eISSN
- 1872-7123
- Publisher
- Elsevier B.V
- Language
- English
- Electronic publication date
- 05/08/2024
- Date published
- 07/2024
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984626141902771
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