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

Song, Cai; Liu, Bai-Ping; Zhang, Yongping; Peng, Zhilan; Wang, JiaJia; Collier, Adam D.; Echevarria, David J.; Savelieva, Katerina V.; Lawrence, Robert F.; Rex, Christopher S.; Meshalkina, Darya A.; Kalueff, Allan V.

doi:10.1016/j.pnpbp.2017.08.021

Cited by 84 publications

(68 citation statements)

References 113 publications

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“…To confirm if shallow water, water changes and overcrowding changed zebrafish stress-regulating systems, we analyzed the effects of these three stressors separately in animals with 6 weeks old. As previously observed in adults (Pavlidis et al, 2013; Song et al, 2018), the acute stressors increased cortisol levels in young animals.…”

Section: Discussionsupporting

confidence: 84%

Moderate early-life stress improves adult zebrafish (Danio rerio) spatial short-term memory but does not affect social and anxiety-like responses

Fontana

Gibbon

Sudwarts

et al. 2020

Preprint

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5Early-life stress (ELS) is defined as a short or chronic period of trauma, environmental or 3 6 social deprivation, which can affect different neurochemical and behavioral patterns during 3 7 adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human 3 8 neurodevelopmental disorders and display translationally relevant behavioral and stress-regulating 3 9systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young 4 0 animals (six weeks post-fertilization), for three consecutive days, to three stressors, and analyzing 4 1 the impact of this on adult zebrafish behavior (sixteen weeks post-fertilization). The ELS impact in 4 2 adults was assessed though analysis of performance on tests of unconditioned memory (free 4 3 movement pattern Y-maze test), exploratory and anxiety-related task (novel tank diving test) and 4 4 social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the 4 5 number of pure alternations compared to pure repetitions in the unconditioned Y-maze task, 4 6suggesting increased spatial short-term memory, but has no effect on shoal cohesion, locomotor 4 7 profile or anxiety-like behavior. Overall, our data suggest that moderate ELS may be linked to 4 8 adaptive flexibility which contributes to build 'resilience' in adult zebrafish by improving short-4 9 term spatial memory performance. 5 0 5 1

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Section: Discussionsupporting

confidence: 84%

Moderate early-life stress improves adult zebrafish (Danio rerio) spatial short-term memory but does not affect social and anxiety-like responses

Fontana

Gibbon

Sudwarts

et al. 2020

Preprint

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“…We demonstrated for the first time that UCS protocol induced several changes in redox homeostasis in the zebrafish brain and revealed that EE has a protective effect against the oxidative stress induced by the UCS protocol. UCS protocol induces several biochemical changes in the zebrafish brain and through sustained activation of the neuroendocrine axis leads to increased cortisol levels (Piato et al, 2011;Manuel et al, 2014;Marcon et al, 2016;Rambo et al, 2017;Song et al, 2017). This was confirmed by the results recently published in our previous study, which showed that the UCS protocol increased cortisol levels while EE for 21 or 28 days prevented this increase (Marcon et al, 2018).…”

Section: Discussionsupporting

confidence: 86%

Peer Review #4 of "Enriched environment prevents oxidative stress in zebrafish submitted to unpredictable chronic stress (v0.1)"

2018

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Background: The enriched environment (EE) is a laboratory housing model that emerged from efforts to minimize the impact of environmental conditions on laboratory animals. Recently, we showed that EE promoted positive effects on behavior and cortisol levels in zebrafish submitted to the unpredictable chronic stress (UCS) protocol. Here, we expanded the characterization of the effects of UCS protocol by assessing parameters of oxidative status in the zebrafish brain and reveal that EE protects against the oxidative stress induced by chronic stress. Methods: Zebrafish were exposed to EE (21 or 28 days) or standard housing conditions and subjected to the UCS protocol for 7 days. Oxidative stress parameters (lipid peroxidation (TBARS), reactive oxygen species (ROS) levels, non-protein thiol (NPSH) and total thiol (SH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured in brain homogenate. Results: Our results revealed that UCS increased lipid peroxidation and ROS levels, while decreased NPSH levels and SOD activity, suggesting oxidative damage. EE for 28 days prevented all changes induced by the UCS protocol, and EE for 21 days prevented the alterations on NPSH levels, lipid peroxidation and ROS levels. Both EE for 21 or 28 days increased CAT activity. Discussion: Our findings reinforce the idea that EE exerts neuromodulatory effects in the zebrafish brain. EE promoted positive effects as it helped maintain the redox homeostasis, which may reduce the susceptibility to stress and its oxidative impact.

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“…Future studies should address the duration or persistence of long-term neuroendocrine and behavioral effects of 7d CUS and whether chronic prazosin treatment administered during the same period as the stressors would circumvent any possible effects of allowing previously stressed animals to adapt back to non-stressed conditions. Other studies have examined the effects of anxiolytic compounds administered concurrent with chronic stress paradigms; for example, in a previous study, zebrafish were exposed to chronic unpredictable stress for five weeks but then were treated with the antidepressant fluoxetine during the last 8 days of the stressor paradigm (Song et al, 2018). Another study exposed zebrafish to chronic unpredictable stress for 14 days but treated with the putative anxiolytic N-acetylcysteine concurrent with the last 7 days of the stress (Mocelin et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have indicated that CUS modeling in zebrafish elicits anxiety-like behaviors in a variety of testing paradigms (Chakravarty et al, 2013;Fulcher et al, 2017;Marcon et al, 2016;Marcon et al, 2018;Piato et al, 2011;Song et al, 2018). CUS also increases wholebody cortisol levels (Manuel et al, 2014;Marcon et al, 2016;Marcon et al, 2018;Piato et al, 2011;Song et al, 2018), although in one report, CUS was shown to increase basal cortisol levels only in male fish but did not significantly alter basal cortisol levels in female fish (Rambo et al, 2017). Thus, the CUS model in zebrafish could be used to examine the efficacy of repurposed compounds and clarify the mechanisms by which these compounds could alleviate physiological dysfunction associated with stress-related conditions.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

O’Daniel

Petrunich-Rutherford

2020

PeerJ

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Post-traumatic stress disorder (PTSD) is often associated with significant neuroendocrine dysfunction and a variety of other symptoms. Today, there are limited efficacious treatment options for PTSD, none of which directly target the dysfunction observed with the hypothalamic-pituitary-adrenal (HPA) axis. The development of new pharmacological treatments is expensive and time consuming; thus, there is utility in repurposing compounds already approved for use in other conditions. One medication in particular that has shown promise for the alleviation of PTSD symptoms is prazosin, an alpha-1 adrenergic receptor antagonist used to treat hypertension. While there have been many studies indicating the efficacy of prazosin in the treatment of PTSD symptoms, no studies fully elucidate mechanisms elicited by this treatment, nor is it clear if prazosin normalizes neuroendocrine dysfunction associated with trauma exposure. The use of zebrafish (Danio rerio) has been growing in popularity, in part, due to the homology of the stress response system with mammals. In this study, the zebrafish model was utilized to determine behavioral and biological changes induced by chronic unpredictable stress (CUS) and how these effects could be modulated by chronic prazosin treatment. The results indicated that 7d of CUS increased anxiety-like behavior in the novel tank test and decreased basal levels of cortisol. Chronic (7d) prazosin treatment decreased anxiety-like behaviors overall but did not appear to affect CUS-induced changes in behavior and basal cortisol levels. This suggests that the clinical effectiveness of prazosin may not normalize dysregulated stress responses prevalent in many patients with PTSD, but that prazosin-induced relief from anxiety in stress-related conditions may involve an alternative mechanism other than by normalizing neuroendocrine dysfunction.

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

Cited by 84 publications

References 113 publications

Moderate early-life stress improves adult zebrafish (Danio rerio) spatial short-term memory but does not affect social and anxiety-like responses

Moderate early-life stress improves adult zebrafish (Danio rerio) spatial short-term memory but does not affect social and anxiety-like responses

Peer Review #4 of "Enriched environment prevents oxidative stress in zebrafish submitted to unpredictable chronic stress (v0.1)"

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

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