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Despite decades of research, we still lack a complete understanding of what factors influence the transition of the necessary and adaptive acute stress response to what has become known as chronic stress. This gap in knowledge has illuminated the necessity for studies that examine the thresholds between these two sides of the stress response. Here, we determine how repeated exposure to acute stressors influences physiological and behavioral responses. In this repeated measures study, house sparrows ( Passer domesticus ) were exposed to a chronic stress protocol. We took physiological and behavioral measurements before, during, and after the protocol. Blood samples were used to assess four aspects of hypothalamic-pituitary-adrenal (HPA) axis function: baseline corticosterone, stress-induced corticosterone, negative feedback, and the maximal capacity to secrete corticosterone. We also assessed bacterial killing capacity and changes in uric acid concentration. Neophobia trials were used to assess behavioral changes throughout the protocol. We found no significant changes in HPA axis regulation in any of the four aspects we tested. However, we found that uric acid concentrations and neophobia significantly decreased after only four days of the chronic stress protocol, while bacterial killing capacity did not decrease until after eight days of exposure. These results indicate that different components of the stress response can be impacted by chronic stress on different timescales. Our results further indicate the importance of assessing multiple aspects of both physiology and behavior in order to understand how exposure to chronic stress may influence ability to cope with future challenges.
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Repeated stimulation of the HPA axis alters white blood cell count without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups
ABSTRACT The hypothalamic–pituitary–adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days. We collected blood at baseline, 2 h and 4 days after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2 h, with effects diminishing at 4 days. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4 days. ACTH decreased neutrophils at 2 h, while decreasing lymphocytes and increasing the neutrophil:lymphocyte ratio at 4 days. These effects were abolished by RU486. Despite alterations in white blood cells, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4 day fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2 h) and chronic (4 days) modulatory effects of HPA activation on white blood cells and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' extraordinary resistance to oxidative stress derived from repeated HPA activation.
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- Award ID(s):
- 1907155
- PAR ID:
- 10300887
- Date Published:
- Journal Name:
- Journal of Experimental Biology
- Volume:
- 224
- Issue:
- 18
- ISSN:
- 0022-0949
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1242/jeb.243198
