skip to main content

This content will become publicly available on March 31, 2023

Title: The Effect of a Combined Fast and Chronic Stress on Body Mass, Blood Metabolites, Corticosterone, and Behavior in House Sparrows (Passer domesticus)
One aspect of the Reactive Scope Model is wear-and-tear, which describes a decrease in an animal’s ability to cope with a stressor, typically because of a period of chronic or repeated stressors. We investigated whether wear-and-tear due to chronic stress would accelerate a transition from phase II to phase III of fasting. We exposed house sparrows (Passer domesticus) to three weeks of daily fasts combined with daily intermittent repeated acute stressors to create chronic stress, followed by two weeks of daily fasts without stressors. We measured circulating glucose, β-hydroxybutyrate (a ketone), and uric acid in both fasted and fed states. We expected birds to be in phase II (high fat breakdown) in a fasted state, but if wear-and-tear accumulated sufficiently, we hypothesized a shift to phase III (high protein breakdown). Throughout the experiment, the birds exhibited elevated β-hydroxybutyrate when fasting but no changes in circulating uric acid, indicating that a transition to phase III did not occur. In both a fasted and fed state, the birds increased glucose mobilization throughout the experiment, suggesting wear-and-tear occurred, but was not sufficient to induce a shift to phase III. Additionally, the birds exhibited a significant decrease in weight, no change in corticosterone, and more » a transient decrease in neophobia with chronic stress. In conclusion, the birds appear to have experienced wear-and-tear, but our protocol did not accelerate the transition from phase II to phase III of fasting. « less
Authors:
; ; ;
Award ID(s):
1655269
Publication Date:
NSF-PAR ID:
10351073
Journal Name:
The Yale journal of biology and medicine
Volume:
95
Issue:
1
Page Range or eLocation-ID:
19-31
ISSN:
0044-0086
Sponsoring Org:
National Science Foundation
More Like this
  1. 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 indicatemore »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.« less
  2. Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale ( n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester ( d -β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degenerationmore »occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.« less
  3. 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 peroxidasemore »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.« less
  4. The wear and tear of adapting to chronic stressors such as racism and discrimination can have detrimental effects on mental and physical health. Here, we investigated the wider implications of everyday racism for relationship quality in an adult sample of 98 heterosexual African American couples. Participants reported on their experiences of racial discrimination and positive and negative affect for 21 consecutive evenings. Using dyadic analyses, we found that independently of age, gender, marital status, income, racial-discrimination frequency, neuroticism, and mean levels of affect, participants’ relationship quality was inversely associated with their partner’s negative affective reactivity to racial discrimination. Associations did not vary by gender, suggesting that the effects of affective reactivity were similar for men and women. These findings highlight the importance of a dyadic approach and call for further research examining the role of everyday racism as a key source of stress in the lives of African American couples.

  5. The rise of mammals after the extinction of the dinosaurs remains one of the most enigmatic intervals in the evolution of mammals. A relatively sparse Paleocene fossil record and confusing interrelationships between taxa means that little is known of the evolution, ecology, and biology of these animals. As a result, the life history of these organisms is completely unstudied, despite likely playing a key role in the ability of these clades to rapidly proliferate and increase in body size in recovering ecosystems. However, intensive collection efforts in the San Juan Basin of New Mexico in the last decade have drastically improved the record of many Paleocene mammals, and offer the first opportunity to address questions about the life history of these animals. Here, we present preliminary results of an in-depth paleohistological analysis of Pantolambda bathmodon, an early, possibly gregarious pantodont, using an ontogenetic series of individuals. Pantodonts were bizarre, herbivorous eutherians of unknown phylogenetic affinity, and were among the first mammal lineages to reach large body sizes in the Paleocene. In examining both dental and skeletal records of growth from the same individuals, including a juvenile still bearing deciduous teeth, our study is among the most comprehensive paleohistological analyses ofmore »any fossil mammal. This intensive approach allows for unprecedented insights into the life history of this species. Neonatal lines in the teeth indicate that the deciduous premolars and the first upper molar were erupted prior to birth, similar to precocious, nidifugous mammals today. Daily incremental lines in the enamel and dentine suggest rapid crown formation times (~45–70 days) and a gestation period of at least 15 weeks. A stress line in the postcranial bones, recording an anomalous decrease in growth towards the end of this individual’s life, may represent the weaning event. In the absence of geochemical evidence, it is unclear which of two stress lines in the teeth corresponds to this event, but these lines occur roughly one and two months after birth, respectively. The weanling perished approximately 2.5 months after birth, weighing about 17 kg. An adult individual exhibiting severe wear on the dentition allows us to estimate maximum longevity in Pantolambda bathmodon at about 7 years. In comparison with life history data on living mammals from the PanTheria dataset, Pantolambda bathmodon had a gestation length and weaning duration below average for a placental of its adult body size (42 kg), but within the range of known variation. However, its lifespan was exceptionally short, falling outside the bounds of comparable living mammals. Together, these lines of evidence suggest a relatively rapid pace of life in Pantolambda bathmodon, despite its relatively large body size. Ongoing sampling of more individuals and geochemical analyses should allow for estimation of time to sexual maturity and help to confirm the identity of the weaning line, completing our picture of the life history of this pioneering species.« less