Psychiatry Res
Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA. Electronic address:
Published: July 2024
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.
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http://dx.doi.org/10.1016/j.psychres.2024.115951 | DOI Listing |
Psychiatry Res
July 2024
Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA. Electronic address:
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.
View Article and Find Full Text PDFUnlabelled: In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents-during the pandemic, the prevalence of obesity increased by ∼37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort.
View Article and Find Full Text PDFBrain Res
February 2022
Department of Psychology, Temple University, United States; Department of Neuroscience Program, Temple University, United States. Electronic address:
Post-weaning social isolation stress has been shown to increase addiction-like behavior in adulthood. These long-term behavioral alterations may be due to long lasting isolation-induced structural changes to neurons in brain regions involved in reward processing. Previous studies have shown that various stressors alter dendritic spine density in the prefrontal cortex (PFC) and the nucleus accumbens, though many of these studies examine the short-term effects of stress, and are primarily conducted in males.
View Article and Find Full Text PDFFront Cell Neurosci
August 2018
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, Qingdao, China.
Disrupted-in-schizophrenia 1 () is a strong candidate susceptibility gene for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar disorder and major depression, all of which are thought to result from interactions between gene mutations and environmental risk factors such as influenza, trauma and stress. Adolescence is a key period susceptible to stress and stress-related mental illnesses. In a previous study, we found that although L100P point mutation mice shows object recognition deficits, their sociability and social memory are relatively normal.
View Article and Find Full Text PDFMol Neurobiol
December 2015
State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
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