Minocycline reduces neurobehavioral deficits evoked by chronic unpredictable stress in adult zebrafish.

Autor: Wang D; School of Pharmacy, Southwest University, Chongqing, China., Wang J; School of Pharmacy, Southwest University, Chongqing, China., Yan D; School of Pharmacy, Southwest University, Chongqing, China., Wang M; School of Pharmacy, Southwest University, Chongqing, China., Yang L; School of Pharmacy, Southwest University, Chongqing, China; Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi'an Jiaotong-Liverpool University (XJTLU), Suzhou, China; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University (XJTLU), Suzhou, China., Demin KA; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia., de Abreu MS; Graduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil; Western Caspian University, Baku, Azerbaijan; Moscow Institute of Physics and Technology, Dolgoprudny, Russia. Electronic address: abreu_murilo@hotmail.com., Kalueff AV; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Center, St. Petersburg, Russia; Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi'an Jiaotong-Liverpool University (XJTLU), Suzhou, China; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University (XJTLU), Suzhou, China; Moscow Institute of Physics and Technology, Dolgoprudny, Russia. Electronic address: avkalueff@gmail.com.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2024 Dec 15; Vol. 1845, pp. 149209. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1016/j.brainres.2024.149209
Abstrakt: Chronic stress-related brain disorders are widespread and debilitating, and often cause lasting neurobehavioral deficits. Minocycline, a common antibiotic and an established inhibitor of microglia, emerges as potential treatment of these disorders. The zebrafish (Danio rerio) is an important emerging model organism in translational neuroscience and stress research. Here, we evaluated the potential of minocycline to correct microglia-mediated behavioral, genomic and neuroimmune responses induced by chronic unpredictable stress (CUS) in adult zebrafish. We demonstrated that CUS evoked overt behavioral deficits in the novel tank, light-dark box and shoaling tests, paralleled by elevated stress hormones (CRH, ACTH and cortisol), and upregulated brain expression of the 'neurotoxic M1' microglia-specific biomarker gene (MHC-2) and pro-inflammatory cytokine genes (IL-1β, IL-6 and IFN-γ). CUS also elevated peripheral (whole-body) pro-inflammatory (IL-1β, IFN-γ) and lowered anti-inflammatory cytokines (IL-4 and IL-10), as well as reduced whole-brain serotonin, dopamine and norepinephrine levels, and increased brain dopamine and serotonin turnover. In contrast, minocycline attenuated most of these effects, also reducing CUS-elevated peripheral levels of IL-6 and IFN-γ. Collectively, this implicates microglia in zebrafish responses to chronic stress, and suggests glial pathways as potential evolutionarily conserved drug targets for treating stress-evoked neuropathogenesis. Our findings also support the growing translational value of zebrafish models for understanding complex molecular mechanisms of brain pathogenesis and its therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: