Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish
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...
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| Veröffentlicht in: | Scientific reports 2020-11, Vol.10 (1), p.19981, Article 19981 |
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| creator | Demin, Konstantin A. Lakstygal, Anton M. Krotova, Nataliya A. Masharsky, Alexey Tagawa, Natsuki Chernysh, Maria V. Ilyin, Nikita P. Taranov, Alexander S. Galstyan, David S. Derzhavina, Ksenia A. Levchenko, Nataliia A. Kolesnikova, Tatiana O. Mor, Mikael S. Vasyutina, Marina L. Efimova, Evgeniya V. Katolikova, Nataliia Prjibelski, Andrey D. Gainetdinov, Raul R. de Abreu, Murilo S. Amstislavskaya, Tamara G. Strekalova, Tatyana Kalueff, Allan V. |
| description | 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. |
| doi_str_mv | 10.1038/s41598-020-75855-3 |
| format | Article |
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Danio rerio
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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. 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33203921</pmid><doi>10.1038/s41598-020-75855-3</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-11, Vol.10 (1), p.19981, Article 19981 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/337/2019 631/378/1457 631/378/1689 631/378/1831 631/45/882 Animal models Animals Antidepressive Agents - pharmacology Anxiety Anxiety - drug therapy Anxiety - physiopathology Arrestin Behavior, Animal - drug effects Behavior, Animal - physiology Brain - drug effects Brain - physiopathology Danio rerio Disease Models, Animal Female Fluoxetine Fluoxetine - pharmacology Genomes Genomic analysis Humanities and Social Sciences Inflammation Male Mental disorders multidisciplinary Nervous system Pathogenesis Science Science (multidisciplinary) Serotonin Stress, Psychological - drug therapy Stress, Psychological - physiopathology Transcriptome - drug effects Transcriptome - physiology Ubiquitin Zebrafish Zebrafish - physiology |
| title | Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T03%3A20%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Understanding%20complex%20dynamics%20of%20behavioral,%20neurochemical%20and%20transcriptomic%20changes%20induced%20by%20prolonged%20chronic%20unpredictable%20stress%20in%20zebrafish&rft.jtitle=Scientific%20reports&rft.au=Demin,%20Konstantin%20A.&rft.date=2020-11-17&rft.volume=10&rft.issue=1&rft.spage=19981&rft.pages=19981-&rft.artnum=19981&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-75855-3&rft_dat=%3Cproquest_pubme%3E2471574403%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471574403&rft_id=info:pmid/33203921&rfr_iscdi=true |