Stress resilience is established during development and is regulated by complement factors

Swaminathan, Amrutha; Gliksberg, Michael; Anbalagan, Savani; Wigoda, Noa; Levkowitz, Gil

doi:10.1016/j.celrep.2022.111973

Cited by 6 publications

(6 citation statements)

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“…We hypothesized that early‐life perturbations of the feedback inhibition of POMC cells might impact stress‐related behaviour. For this, we subjected dexamethasone treated larvae to an osmotic stressful challenge that induces freezing behaviour, a direct indicator of stress 15,18 . Upon treatment with dexamethasone, we observed significantly reduced locomotion following a stressful challenge (Figure 4A; p < .0001 comparing control and dexamethasone following stress, n = 8 unstressed, n = 32 stressed, two‐way ANOVA followed by Sidak's post hoc multiple comparisons test).…”

Section: Resultsmentioning

confidence: 98%

“…For this, we subjected dexamethasone treated larvae to an osmotic stressful challenge that induces freezing behaviour, a direct indicator of stress. 15,18 Upon treatment with dexamethasone, we observed significantly reduced locomotion following a stressful challenge (Figure 4A; p < .0001 comparing control and dexamethasone following stress, n = 8 unstressed, n = 32 stressed, two-way ANOVA followed by Sidak's post hoc multiple comparisons test). To further substantiate our claim, we used an additional zebrafish larval behavioural assay:…”

Section: Dysregulated Glucocorticoid Levels Impact Stress-related Beh...mentioning

confidence: 93%

“…The assay was performed as previously described 15 . Briefly, 6 dpf larvae were transferred to a well with 50% artificial seawater (stressed) or fresh Danieau's medium (unstressed) for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…The assay was performed as previously described. 15 Briefly, 6 dpf larvae were transferred to a well with 50% artificial seawater (stressed) or fresh Danieau's medium (unstressed) for 20 min. Following this, they were individually transferred to single wells of a 96-well plate with fresh Danieau's medium.…”

Section: Stress-response Assaymentioning

confidence: 99%

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Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Peles

Swaminathan

Levkowitz

2023

J Neuroendocrinology

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Corticotrophs are intermediaries in the hypothalamic–pituitary–adrenal (HPA) axis, which plays a crucial role in stress response in vertebrates. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)‐expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we studied the effect of glucocorticoids on the development of POMC‐expressing cells in the zebrafish pituitary. The development of POMC cells showed a steady increase in numbers between 2–6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in corticotroph cell number, mimicking greater feedback control due to increased cortisol levels. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety‐like and stress‐coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress‐responsive behaviour.

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Section: Resultsmentioning

confidence: 98%

Section: Dysregulated Glucocorticoid Levels Impact Stress-related Beh...mentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Stress-response Assaymentioning

confidence: 99%

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Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Peles

Swaminathan

Levkowitz

2023

J Neuroendocrinology

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“…Such research is highlighting not only how pathways of toxicity are known to be conserved but that many exposure agents operate via the same pathway (i.e., relatively nonspecific) . This provides opportunities for the application of nonmammalian animal models used in fundamental biomedical research to define the molecular mechanisms of exposures (e.g., Drosophila melanogaster, Danio rerio, Caenorhabditis elegans) including for social stress and diet . Such research should help to prioritize hypothesis-driven laboratory testing from exposome cohorts and has implications for identifying exposures of concern across environmental to human health perspectives.…”

Section: Understanding Molecular Mechanisms Underlying Exposures In T...mentioning

confidence: 99%

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Foreman,

Warth,

Hessel

et al. 2024

Environ. Sci. Technol.

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Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

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Early stress exposure on zebrafish development: effects on survival, malformations and molecular alterations

Valcarce,

Sellés-Egea,

Riesco

et al. 2024

Fish Physiol Biochem

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The effects of stress during early vertebrate development can be especially harmful. Avoiding stressors in fish larvae is essential to ensure the health of adult fish and their reproductive performance and overall production. We examined the consequences of direct exposure to successive acute stressors during early development, including their effects on miR-29a and its targets, survival, hatching and malformation rates, larval behaviour and cartilage and eye development. Our aim was to shed light on the pleiotropic effects of early-induced stress in this vertebrate model species. Our results showed that direct exposure to successive acute stressors during early development significantly upregulated miR-29a and downregulated essential collagen transcripts col2a1a, col6a2 and col11a1a, decreased survival and increased malformation rates (swim bladder, otoliths, cardiac oedema and ocular malformations), promoting higher rates of immobility in larvae. Our results revealed that stress in early stages can induce different eye tissular architecture and cranioencephalic cartilage development alterations. Our research contributes to the understanding of the impact of stressful conditions during the early stages of zebrafish development, serving as a valuable model for vertebrate research. This holds paramount significance in the fields of developmental biology and aquaculture and also highlights miR-29a as a potential molecular marker for assessing novel larval rearing programmes in teleost species.

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Stress resilience is established during development and is regulated by complement factors

Cited by 6 publications

References 48 publications

Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Early stress exposure on zebrafish development: effects on survival, malformations and molecular alterations

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