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      Modeling consequences of prolonged strong unpredictable stress in zebrafish: Complex effects on behavior and physiology.

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          Abstract

          Chronic stress is the major pathogenetic factor of human anxiety and depression. Zebrafish (Danio rerio) have become a novel popular model species for neuroscience and CNS drug discovery. The utility of zebrafish for mimicking human affective disorders is also rapidly growing. Here, we develop a new zebrafish model of clinically relevant, prolonged unpredictable chronic stress (PUCS). The 5-week PUCS induced overt anxiety-like and motor retardation-like behaviors in adult zebrafish, also elevating whole-body cortisol and proinflammatory cytokines interleukins IL-1β and IL-6. PUCS also elevated whole-body levels of the anti-inflammatory cytokine IL-10 and increased the density of dendritic spines in telencephalic neurons. Chronic treatment with an antidepressant fluoxetine (0.1mg/L for 8days) normalized the behavioral and endocrine phenotypes, as well as stress-elevated IL-1β and IL-6 levels, similar to clinical and rodent data. The CNS expression of the bdnf gene, the two genes of its receptors (trkB, p75), and the gfap gene of glia biomarker, the glial fibrillary acidic protein, was unaltered in all three groups. However, stress elevated whole-body BDNF levels and telencephalic dendritic spine density (which were corrected by fluoxetine), thereby somewhat differing from the effects of chronic stress in rodents. Together, these findings support zebrafish as a useful in-vivo model of chronic stress, also calling for further cross-species studies of both shared and distinct neurobiological responses to chronic stress.

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          Author and article information

          Journal
          Prog. Neuropsychopharmacol. Biol. Psychiatry
          Progress in neuro-psychopharmacology & biological psychiatry
          Elsevier BV
          1878-4216
          0278-5846
          Aug 25 2017
          Affiliations
          [1 ] Institute for Marine Drugs and Nutrition, Zhanjiang City Key Laboratory, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 3452001, Guangdong, China; Graduate Institute of Neural and Cognitive Science, China Medical University and Hospital, Taichung 00001, Taiwan. Electronic address: Cai.Song@dal.ca.
          [2 ] Institute for Marine Drugs and Nutrition, Zhanjiang City Key Laboratory, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 3452001, Guangdong, China.
          [3 ] ZENEREI Institute and the International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell 70458, LA, USA.
          [4 ] ZENEREI Institute and the International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell 70458, LA, USA; Department of Psychology, University of Southern Mississippi, Hattiesburg 39406, MS, USA.
          [5 ] Afraxis, Inc. 6605 Nancy Ridge Rd. Suite 224, San Diego 92121, CA, USA.
          [6 ] Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 3960002, Russia.
          [7 ] Institute for Marine Drugs and Nutrition, Zhanjiang City Key Laboratory, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 3452001, Guangdong, China; ZENEREI Institute and the International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell 70458, LA, USA; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 3960002, Russia; Ural Federal University, Ekaterinburg 620002, Russia. Electronic address: avkalueff@gmail.com.
          Article
          S0278-5846(17)30459-1
          10.1016/j.pnpbp.2017.08.021
          28847526
          5acf0926-1785-40c8-946d-0b8725507f49

          Antidepressant,BDNF,Chronic stress,Experimental model,Zebrafish

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