Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish.

Autor: Demin KA; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia. deminkasci@gmail.com.; Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, Saint-Petersburg, Russia. deminkasci@gmail.com., Lakstygal AM; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Krotova NA; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia.; Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, Saint-Petersburg, Russia., Masharsky A; Core Facility Centre for Molecular and Cell Technologies, St. Petersburg State University, Saint-Petersburg, Russia., Tagawa N; Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan., Chernysh MV; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Ilyin NP; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Taranov AS; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Galstyan DS; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia.; Laboratory of Preclinical Bioscreening, Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, Pesochny, Russia., Derzhavina KA; Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, Saint-Petersburg, Russia., Levchenko NA; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Kolesnikova TO; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Mor MS; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Vasyutina ML; Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, Saint-Petersburg, Russia., Efimova EV; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., Katolikova N; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia.; Institute of Cytology RAS, Saint-Petersburg, Russia., Prjibelski AD; Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, Saint-Petersburg, Russia., Gainetdinov RR; Institute of Translational Biomedicine, St. Petersburg State University, University Emb. 7-9, Saint-Petersburg, Russia., de Abreu MS; University of Passo Fundo, Passo Fundo, Brazil., Amstislavskaya TG; Laboratory of Biopsychiatry, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.; School of Medicine and Psychology, Novosibirsk State University, Novosibirsk, Russia., Strekalova T; Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.; Division of Molecular Psychiatry, Centre of Mental Health, University of Würzburg, Würzburg, Germany., Kalueff AV; School of Pharmacy, Southwest University, Chongqing, China. avkalueff@gmail.com.; Ural Federal University, Ekaterinburg, Russia. avkalueff@gmail.com.; Laboratory of Cell and Molecular Biology and Neurobiology, Moscow Institute of Physics and Technology, Dolgoprudny, Russia. avkalueff@gmail.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Nov 17; Vol. 10 (1), pp. 19981. Date of Electronic Publication: 2020 Nov 17.
DOI: 10.1038/s41598-020-75855-3
Abstrakt: Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.
Databáze: MEDLINE