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Study · Animal study (in vivo) · mouse · 2024

4 results

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

Jin M, Zhang S, Huang B, Li L, Liang H, Ni A, Han L, Liang P, Liu J, Shi H, Lv P

Brain and behavior1 Mar 2024Cited by 10 (Europe PMC)

PMID38444330 (opens in a new tab)DOI10.1002/brb3.3448 (opens in a new tab)PepBankPUB-38444330
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Summary

IntroductionTreatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice.MethodsSixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment.ResultsThree weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy.ConclusionThe antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In chronically stressed mice, dulaglutide reversed depressive-like behavior.

    In plain wordsIn mice with chronic stress, dulaglutide reduced depressive-like behavior compared with vehicle.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    DecreaseDepressive-like behavior
    Study

    micen: not reported in source

    Chronic mild stress
    Comparator
    CMS+Vehicle
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mice).

    Source sentences

    Summary
    Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks.
    1 context sentence
    Summary · context
    Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group).
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In chronically stressed mice, dulaglutide did not reverse anxiety-like behavior.

    In plain wordsIn mice with chronic stress, dulaglutide did not reduce anxiety-like behavior compared with vehicle.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    No significant changeAnxiety-like behavior
    Study

    micen: not reported in source

    Chronic mild stress
    Comparator
    CMS+Vehicle
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mice).

    Source sentences

    Summary
    Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks.
    1 context sentence
    Summary · context
    Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group).
  3. 03AnimalAnimal study (in vivo)Mechanism

    In chronically stressed mice, 46 hippocampal metabolites differed between high-dose dulaglutide and vehicle groups.

    In plain wordsIn mice with chronic stress, 46 hippocampal metabolites differed between high-dose dulaglutide and vehicle groups.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedHippocampal metabolite profile
    Study

    micen: not reported in source

    Chronic mild stress
    Comparator
    CMS+Vehicle
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.6 mg/kg · 3 weeksAs given in this study (mice).

    Source sentences

    Summary
    The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice.
    1 context sentence
    Summary · context
    Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group).
  4. 04AnimalAnimal study (in vivo)Mechanism

    In stressed mice receiving dulaglutide, analysis identified disturbances in lipid, amino acid, energy, and tryptophan metabolism.

    In plain wordsIn mice with stress receiving dulaglutide, analysis identified disturbances in lipid, amino acid, energy, and tryptophan metabolism.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedMetabolic pathway profile
    Study

    micen: not reported in source

    Chronic mild stress
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mice).

    Source sentences

    Summary
    Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy.
    1 context sentence
    Summary · context
    Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

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Terms as the source lists them.

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