Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Minocycline reduces neurobehavioral deficits evoked by chronic unpredictable stress in adult zebrafish. / Wang, D.; Wang, J.; Yan, D.; Wang, M.; Yang, L.; Demin, K.A.; de Abreu, M.S.; Kalueff, A.V.
в: Brain Research, Том 1845, 01.12.2024.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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 - 2024/12/1
Y1 - 2024/12/1
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
UR - https://www.mendeley.com/catalogue/0df2f05c-80e5-34d1-b04e-88cf11fd490c/
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 -
ID: 126165162