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Comparative evaluation of two chronic stress models in zebrafish for advancing depression research.

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Τίτλος: Comparative evaluation of two chronic stress models in zebrafish for advancing depression research.
Συγγραφείς: Tripathy C; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India., Dhaygude SS; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India., Vijay V; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India., Mondal A; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India., Soren K; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India., Kumar A; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Chakravarty S; Applied Biology, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India. Electronic address: sumanachak@csiriict.in.
Πηγή: Physiology & behavior [Physiol Behav] 2026 Oct 15; Vol. 315, pp. 115453. Date of Electronic Publication: 2026 Jul 24.
Τύπος έκδοσης: Journal Article; Comparative Study
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: United States NLM ID: 0151504 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-507X (Electronic) Linking ISSN: 00319384 NLM ISO Abbreviation: Physiol Behav Subsets: MEDLINE
Imprint Name(s): Publication: New York NY : Elsevier Science
Original Publication: Oxford, Eng., Long Island City, Pergamon Press.
Ιατρικοί όροι (MeSH): Stress, Psychological*/physiopathology , Depression*/physiopathology , Disease Models, Animal*, Aggression/psychology ; Animals ; Zebrafish ; Male ; Female ; Chronic Disease
Περίληψη: Depression is a debilitating neuropsychiatric disorder, and the failure of many antidepressants in clinical trials reflects the limited predictive validity of preclinical models. Therefore, a comparative evaluation of animal models that recapitulate the behavioral and molecular features of depression is essential for improving translational relevance. This study evaluated the utility of two chronic stress paradigms in zebrafish for modeling depression-like states. A modified Chronic Stress model termed Chronic Aggression Stress (CAgS) was developed and compared with the established Chronic Unpredictable Stress (CUS) model. In the CAgS paradigm, zebrafish were subjected to daily encounters with an aggressive cichlid for five days, while the CUS paradigm involved ten distinct stressors administered unpredictably twice daily for 10 days. Behavioral outcomes were assessed using the novel tank test, scototaxis, and threat response test. Molecular changes were examined by RT-qPCR, western blotting, and immunofluorescence. Both stress models induced robust depression-like phenotypes in adult zebrafish. CAgS produced consistent behavioral deficits, including reduced locomotion, increased anxiety-like behavior, and enhanced passive defensive responses across sexes, whereas CUS elicited divergent behavioral trajectories. At the molecular level, CAgS triggered a pronounced pro-inflammatory state characterized by elevated microglial activation and disrupted neurotrophic signaling. In contrast, CUS produced a more heterogeneous response, including sex-specific regulation of inflammatory cytokines and neurotrophic pathways. Both stress paradigms also showed astroglial activation and altered cellular proliferation. These findings demonstrate that both CAgS and CUS paradigms induce depressive-like phenotypes in zebrafish, with CUS uniquely revealing sex-specific behavioral and molecular alterations, highlighting their complementary utility for investigating depressive pathophysiology.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
Contributed Indexing: Keywords: Chronic aggression stress; Chronic unpredictable stress; Depressive phenotypes; Inflammatory factors; Neurotrophic factors; Sex difference
Entry Date(s): Date Created: 20260724 Date Completed: 20260807 Latest Revision: 20260807
Update Code: 20260808
DOI: 10.1016/j.physbeh.2026.115453
PMID: 42498236
Βάση Δεδομένων: MEDLINE
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  Data: Depression is a debilitating neuropsychiatric disorder, and the failure of many antidepressants in clinical trials reflects the limited predictive validity of preclinical models. Therefore, a comparative evaluation of animal models that recapitulate the behavioral and molecular features of depression is essential for improving translational relevance. This study evaluated the utility of two chronic stress paradigms in zebrafish for modeling depression-like states. A modified Chronic Stress model termed Chronic Aggression Stress (CAgS) was developed and compared with the established Chronic Unpredictable Stress (CUS) model. In the CAgS paradigm, zebrafish were subjected to daily encounters with an aggressive cichlid for five days, while the CUS paradigm involved ten distinct stressors administered unpredictably twice daily for 10 days. Behavioral outcomes were assessed using the novel tank test, scototaxis, and threat response test. Molecular changes were examined by RT-qPCR, western blotting, and immunofluorescence. Both stress models induced robust depression-like phenotypes in adult zebrafish. CAgS produced consistent behavioral deficits, including reduced locomotion, increased anxiety-like behavior, and enhanced passive defensive responses across sexes, whereas CUS elicited divergent behavioral trajectories. At the molecular level, CAgS triggered a pronounced pro-inflammatory state characterized by elevated microglial activation and disrupted neurotrophic signaling. In contrast, CUS produced a more heterogeneous response, including sex-specific regulation of inflammatory cytokines and neurotrophic pathways. Both stress paradigms also showed astroglial activation and altered cellular proliferation. These findings demonstrate that both CAgS and CUS paradigms induce depressive-like phenotypes in zebrafish, with CUS uniquely revealing sex-specific behavioral and molecular alterations, highlighting their complementary utility for investigating depressive pathophysiology.<br /> (Copyright © 2026 Elsevier Inc. All rights reserved.)
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  Data: Declaration of competing interest The authors declare that they have no conflict of interest.
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