Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

Chakravarty, Sumana; Reddy, Bommana Raghunath; Sudhakar, Sreesha R.; Saxena, Sandeep; Das, Tapatee; Vuppalapaty, Meghah; Swamy, Cherukuvada V. Brahmendra; Kumar, Arvind; Idris, Mohammed M.

doi:10.1371/journal.pone.0063302

Cited by 155 publications

(139 citation statements)

References 63 publications

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“…In the present study, UCS induced a downregulation of both gr mRNAs in the POA while mr transcript amount was unaffected. A reduced expression of gr1 and gr2 and an increase in crf mRNA is in line with previous observations in zebrafish (Chakravarty et al, 2013;Piato et al, 2011) and trout (Doyon et al, 2005). Low levels of gr1 and gr2 may protect neurones from high levels of cortisol during chronic stress.…”

Section: Poasupporting

confidence: 92%

Stress in Atlantic salmon: response to unpredictable chronic stress

Madaro

Olsen

Kristiansen

et al. 2015

Journal of Experimental Biology

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Combinations of stressors occur regularly throughout an animal's life, especially in agriculture and aquaculture settings. If an animal fails to acclimate to these stressors, stress becomes chronic, and a condition of allostatic overload arises with negative results for animal welfare. In the current study, we describe effects of exposing Atlantic salmon parr to an unpredictable chronic stressor (UCS) paradigm for 3 weeks. The paradigm involves exposure of fish to seven unpredictable stressors three times a day. At the end of the trial, experimental and control fish were challenged with yet another novel stressor and sampled before and 1 h after that challenge. Plasma cortisol decreased steadily over time in stressed fish, indicative of exhaustion of the endocrine stress axis. This was confirmed by a lower cortisol response to the novel stressor at the end of the stress period in chronically stressed fish compared with the control group. In the preoptic area (POA) and pituitary gland, chronic stress resulted in decreased gene expression of 11βhsd2, gr1 and gr2 in the POA and increased expression of those genes in the pituitary gland. POA crf expression and pituitary expression of pomcs and mr increased, whereas interrenal gene expression was unaffected. Exposure to the novel stressor had no effect on POA and interrenal gene expression. In the pituitary, crfr1, pomcs, 11βhsd2, grs and mr were downregulated. In summary, our results provide a novel overview of the dynamic changes that occur at every level of the hypothalamicpituitary gland-interrenal gland (HPI) axis as a result of chronic stress in Atlantic salmon.

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Section: Poasupporting

confidence: 92%

Stress in Atlantic salmon: response to unpredictable chronic stress

Madaro

Olsen

Kristiansen

et al. 2015

Journal of Experimental Biology

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“…This weak effect of UCS on crf expression seems at variance with the literature as crf expression has been shown to strongly increase following UCS (Chakravarty et al, 2013;Piato et al, 2011). The reasons underlying these differences may be related to sampling procedures: while we sampled the telencephalon specifically, others sampled the whole brain (Chakravarty et al, 2013;Piato et al, 2011).…”

Section: Research Articlementioning

confidence: 57%

“…An upcoming research area is the use of zebrafish as a model to study the effects of chronic stress on brain and behaviour in relation to depression, anxiety and other mood-related disorders (Chakravarty et al, 2013;Gerlai, 2010a;Gerlai, 2010b;Norton, 2013;Piato et al, 2011;Stewart et al, 2014). Zebrafish may be of interest for chronic stress research as they express two glucocorticoid receptors (GR), GRα and GRβ, as humans do but not rodents (Schaaf et al, 2009;Schoonheim et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen Long-Fin zebrafish (Danio rerio Hamilton): stronger effects in the resting phase than in the active phase

Manuel

Gorissen

Zethof

et al. 2014

Journal of Experimental Biology

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Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in glucocorticoid resistance and depression.

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“…In the light/dark test, the preference for a black compartment over a white one, associated with risk assessment behaviours, erratic swimming, thigmotaxis, and freezing is interpreted as defensive behaviour (Maximino et al, 2010b). Moreover, a relationship between stress and behaviour in these tests is established, as both acute (Giacomini et al, 2016) and chronic (Chakravarty et al, 2013;Marcon et al, 2016) stress increases defensive behaviour in these assays, and exposure to the apparatuses induce cortisol levels (Kysil et al, 2017). A causal link between neuroendocrine and behavioural responses to stress has not been ascertained; since these are modulated by monoamines, these neurotransmitters could link both functions.…”

Section: Monoaminergic Innervation In Teleostsmentioning

confidence: 99%

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

Soares

Maximino

2018

Preprint

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Animal-focused research has been crucial for scientific advancement however, in this matter, rodents are still taking a starring role. Coming out from merely being supportive of evidence found in rodents, the use of fish models has slowly taken a more central role and expanded its overall contributions in areas such as social sciences, evolution, physiology, and recently in translational medical research. In neurosciences, zebrafish has been widely adopted, contributing to our understanding of the genetic control of brain processes, and the effects of pharmacological manipulations. However, discussion continues regarding the paradox of function versus structure, when fish and mammals are compared, and on the potentially evolutionarily conserved nature of behaviour across fish species. From the behavioural stand point we explored aversive/stress and social behaviour in selected fish models, and refer to the extensive contributions of stress and monoaminergic systems. We suggest that, in spite of marked neuroanatomical differences between fish and mammals, stress and sociality are conserved at the behavioural and molecular levels. We also suggest that stress and sociality are mediated by monoamines in predictable and non-trivial ways, and that monoamines could "bridge" the relationship between stress and social behaviour. To reconcile the level of divergence with the level of similarity, we need neuroanatomical, pharmacological, behavioural, and ecological studies conducted in the laboratory and in nature.These areas need to add to each other to enhance our understanding of fish behaviour and ultimately how this all may translate to better model systems for translational studies.

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Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

Cited by 155 publications

References 63 publications

Stress in Atlantic salmon: response to unpredictable chronic stress

Stress in Atlantic salmon: response to unpredictable chronic stress

Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen Long-Fin zebrafish (Danio rerio Hamilton): stronger effects in the resting phase than in the active phase

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

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