TY - JOUR
T1 - Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish
AU - Demin, K.A.
AU - Lakstygal, A.M.
AU - Krotova, N.A.
AU - Masharsky, A.
AU - Tagawa, N.
AU - Chernysh, M.V.
AU - Ilyin, N.P.
AU - Taranov, A.S.
AU - Galstyan, D.S.
AU - Derzhavina, K.A.
AU - Levchenko, N.A.
AU - Kolesnikova, T.O.
AU - Mor, M.S.
AU - Vasyutina, M.L.
AU - Efimova, E.V.
AU - Katolikova, N.
AU - Prjibelski, A.D.
AU - Gainetdinov, R.R.
AU - de Abreu, M.S.
AU - Amstislavskaya, T.G.
AU - Strekalova, T.
AU - Kalueff, A.V.
PY - 2020/11/17
Y1 - 2020/11/17
N2 - 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.
AB - 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.
KW - animal-models
KW - anxiety-like behavior
KW - chronic mild stress
KW - depression-like behavior
KW - gene set enrichment
KW - inflammatory markers
KW - monoamine levels
KW - neuroscience research
KW - neurotransmitter systems
KW - pituitary-adrenal axis
KW - GENE SET ENRICHMENT
KW - CHRONIC MILD STRESS
KW - ANXIETY-LIKE BEHAVIOR
KW - INFLAMMATORY MARKERS
KW - NEUROTRANSMITTER SYSTEMS
KW - DEPRESSION-LIKE BEHAVIOR
KW - ANIMAL-MODELS
KW - NEUROSCIENCE RESEARCH
KW - MONOAMINE LEVELS
KW - PITUITARY-ADRENAL AXIS
U2 - 10.1038/s41598-020-75855-3
DO - 10.1038/s41598-020-75855-3
M3 - Article
C2 - 33203921
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19981
ER -