TY - JOUR

T1 - Minocycline reduces neurobehavioral deficits evoked by chronic unpredictable stress in adult zebrafish

AU - Wang, D.

AU - Wang, J.

AU - Yan, D.

AU - Wang, M.

AU - Yang, L.

AU - Demin, K.A.

AU - de Abreu, M.S.

AU - Kalueff, A.V.

N1 - Export Date: 19 October 2024 CODEN: BRREA Адрес для корреспонденции: de Abreu, M.S.; Graduate Program in Health Sciences, Brazil; эл. почта: abreu_murilo@hotmail.com Адрес для корреспонденции: Kalueff, A.V.; School of Science, China; эл. почта: avkalueff@gmail.com Химические вещества/CAS: 3,4 dihydroxyphenylacetic acid, 102-32-9; 5 hydroxyindoleacetic acid, 1321-73-9, 54-16-0; caspase 3, 169592-56-7; caspase 9, 180189-96-2; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; corticotropin releasing factor, 9015-71-8, 178359-01-8, 79804-71-0, 86297-72-5, 86784-80-7; dopamine, 51-61-6, 62-31-7; gamma interferon, 82115-62-6; hydrocortisone, 50-23-7; minocycline, 10118-90-8, 11006-27-2, 13614-98-7; serotonin, 50-67-9 Сведения о финансировании: Xi’an Jiaotong-Liverpool University, XJTLU Сведения о финансировании: Ministry of Education and Science of the Russian Federation, Minobrnauka, FSMG-2021-0006, 075-03-2024-117, 17.01.2024 Сведения о финансировании: Ministry of Education and Science of the Russian Federation, Minobrnauka Сведения о финансировании: 95443748 Текст о финансировании 1: DW and JW were supported by the Zebrafish Platform Construction Fund from the Southwest University (Chongqing, China). The research was also supported by St. Petersburg State University budget funds (PURE Project 95443748 ). AVK is presently supported by the School of Science and Suzhou Key Laboratory of Neurobiology and Cell Signaling of Xi\u2019an Jiaotong-Liverpool University (Suzhou, China). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Текст о финансировании 2: This study was supported by the Ministry of Science and Higher Education of Russian Federation (FSMG-2021-0006, 'Digital technologies for solving problems of quantitative medicine', agreement 075-03-2024-117 of 17.01.2024). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2024

Y1 - 2024

N2 - 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. © 2024 Elsevier B.V.

AB - 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. © 2024 Elsevier B.V.

KW - Microglia

KW - Minocycline

KW - Neuroinflammation

KW - Stress-related disorders

KW - Zebrafish

KW - 3,4 dihydroxyphenylacetic acid

KW - 5 hydroxyindoleacetic acid

KW - antigen

KW - caspase 3

KW - caspase 9

KW - CD11b antigen

KW - cd206 antigen

KW - corticotropin

KW - corticotropin releasing factor

KW - dopamine

KW - early growth response factor 2

KW - gamma interferon

KW - glucocorticoid receptor

KW - hydrocortisone

KW - interleukin 10

KW - interleukin 1beta

KW - interleukin 4

KW - interleukin 6

KW - messenger RNA

KW - mineralocorticoid

KW - minocycline

KW - protein Bax

KW - serotonin

KW - serotonin 1A receptor

KW - unclassified drug

KW - adult

KW - animal experiment

KW - animal model

KW - animal tissue

KW - Article

KW - behavior disorder

KW - brain

KW - chronic unpredictable stress

KW - controlled study

KW - enzyme linked immunosorbent assay

KW - female

KW - gene expression

KW - high performance liquid chromatography

KW - immune response

KW - male

KW - microglia

KW - neuropathology

KW - nonhuman

KW - real time polymerase chain reaction

KW - serotonin level

KW - upregulation

KW - zebra fish

U2 - 10.1016/j.brainres.2024.149209

DO - 10.1016/j.brainres.2024.149209

M3 - статья

VL - 1845

JO - Molecular Brain Research

JF - Molecular Brain Research

SN - 0006-8993

ER -