Telomere shortening is associated with corticosterone stress response in adult barn swallows

February 21, 2022 0 Comments

  • When vertebrates face stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, generating a rapid increase in circulating glucocorticoid (GC) stress hormones followed by a return to baseline levels. However, repeated activation of HPA axis may lead to increase in oxidative stress. One target of oxidative stress is telomeres, nucleoprotein complexes at the end of chromosomes that shorten at each cell division.
  • The susceptibility of telomeres to oxidizing molecules has led to the hypothesis that increased GC levels boost telomere shortening, but studies on this link are scanty. We studied if, in barn swallows Hirundo rustica, changes in adult erythrocyte telomere length between 2 consecutive breeding seasons are related to corticosterone (CORT) (the main avian GC) stress response induced by a standard capture-restraint protocol.
  • Within-individual telomere length did not significantly change between consecutive breeding seasons. Second-year individuals showed the highest increase in circulating CORT concentrations following restraint. Moreover, we found a decline in female stress response along the breeding season. In addition, telomere shortening covaried with the stress response: a delayed activation of the negative feedback loop terminating the stress response was associated with greater telomere attrition. Hence, among-individual variation in stress response may affect telomere dynamics.

Context dependent variation in corticosterone and phenotypic divergence of Rana arvalis populations along an acidification gradient

Background: Physiological processes, as immediate responses to the environment, are important mechanisms of phenotypic plasticity and can influence evolution at ecological time scales. In stressful environments, physiological stress responses of individuals are initiated and integrated via the release of hormones, such as corticosterone (CORT). In vertebrates, CORT influences energy metabolism and resource allocation to multiple fitness traits (e.g. growth and morphology) and can be an important mediator of rapid adaptation to environmental stress, such as acidification. The moor frog, Rana arvalis, shows adaptive divergence in larval life-histories and predator defense traits along an acidification gradient in Sweden. Here we take a first step to understanding the role of CORT in this adaptive divergence. We conducted a fully factorial laboratory experiment and reared tadpoles from three populations (one acidic, one neutral and one intermediate pH origin) in two pH treatments (Acid versus Neutral pH) from hatching to metamorphosis. We tested how the populations differ in tadpole CORT profiles and how CORT is associated with tadpole life-history and morphological traits.
Results: We found clear differences among the populations in CORT profiles across different developmental stages, but only weak effects of pH treatment on CORT. Tadpoles from the acid origin population had, on average, lower CORT levels than tadpoles from the neutral origin population, and the intermediate pH origin population had intermediate CORT levels. Overall, tadpoles with higher CORT levels developed faster and had shorter and shallower tails, as well as shallower tail muscles.
Conclusions: Our common garden results indicate among population divergence in CORT levels, likely reflecting acidification mediated divergent selection on tadpole physiology, concomitant to selection on larval life-histories and morphology. However, CORT levels were highly environmental context dependent. Jointly these results indicate a potential role for CORT as a mediator of multi-trait divergence along environmental stress gradients in natural populations. At the same time, the population level differences and high context dependency in CORT levels suggest that snapshot assessment of CORT in nature may not be reliable bioindicators of stress.

Maternal separation in the light or dark phase of the circadian cycle has different effects on the corticosterone levels and anxiety-like behavior in male adult rats

  • Maternal care in early life is essential for the growth and development of an offspring. The light phase of the circadian cycle is the dam’s most caring phase for her pups. Therefore, we hypothesized that, in the long term, maternal separation (an early-life stress model) in the light phase can be more deleterious than maternal separation in the dark phase.
  • This study aims to compare the effects of maternal separation in the dark or light phase of the circadian cycle on the behavioral and physiological parameters of adult male Wistar rats. From the first to the fourteenth day of life, litters were separated from their mothers for six hours, forming the following experimental groups: Control (C), Maternal Separation in the Light (MSL), and Maternal Separation in the Dark (MSD).
  • After weaning, these groups were left undisturbed until the start of behavioral tests in adulthood. Behavioral measures (standard diet intake, palatable diet intake, and anxiety-like behavior in the elevated plus maze), as well as retroperitoneal adipose tissue weight, and corticosterone levels in response to feeding stress, were assessed between the ages of 120 and 180 days. The results showed that, in adulthood, the food intake after an eight-hour fast or feeding stress had not changed. Anxiety behavior was analyzed by measuring time in the open or closed arms of the elevated plus-maze.
  • The corticosterone levels were measured after food stress, and quantified by using the enzyme-linked immunosorbent assay (ELISA) method. The retroperitoneal adipose tissue weight was also measured. The MSD group presented higher corticosterone levels (MSD = 173.9±12.7) when compared to the C (4.21 ± 0.3) and MSL (4.25 ± 0.28, p < 0.001) groups. In the anxiety test, we observed that the duration in the open arm was shorter for the MSL group (27.4 ± 3.7) compared to the control (112.9 ± 9.6, p < 00.1). There was no change in the MSD group compared to the control, with regard to the time spent in the open arm of the maze.
  • An effect of maternal separation on the consumption of a palatable diet was observed. There was an increase in the palatable diet intake in the MSL (16.3 ± 1.9) and MSD (15.7 ± 0.5) groups compared to the control (11.4 ± 1.2, p < 0.05). In response to stress and food deprivation, there was no difference between groups in food consumption. The adipose tissue weight was higher in the MSD group (7.12 ± 0.29) compared to the control (4.21 ± 0.3) and MSL (4.25 ± 0.28, p < 0.001) groups.
  • Based on the results observed, we concluded that the light-phase stress is more detrimental to emotional behavior during the first two weeks of life, and the dark-phase stress is more detrimental to Hypothalamus-Pituitary-Adrenal (HPA)-axis functioning. Furthermore, the higher intake of a palatable diet could be interpreted as a coping behavior to these early stress-related modifications.

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RNA-seq based transcriptome analysis of ethanol extract of saffron protective effect against corticosterone-induced PC12 cell injury

Background: At present, oral antidepressants are commonly used in the clinical treatment of depression. However, the current drug treatment may lead to more serious adverse reactions. Therefore, we focus on Chinese traditional medicine, trying to find an effective and safe alternative or complementary medicine. Crocus sativus (saffron) is a traditional Chinese herbal medicine, which is typically used in the clinic to regulate anxiety, insomnia, amnesia, and other mental disorder. The study aimed to explore the neuroprotective effect of ethanol extract of saffron (EES) on corticosterone (CORT)- induced injury in PC12 cells and further explored its potential mechanism.
Methods: The authenticity of saffron and the active components of EES were identified by a water test and ultra-performance liquid chromatography-time of flight mass spectrometry system. The screening of cytotoxicity for PC12 cells was incubated with EES in different concentrations for 24 h, and the protective efficacy of EES on CORT (500 μM) -induced PC12 cell injury, cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The differentially expressed genes (DEGs) of EES-protected PC12 cells were analyzed using the RNA-seq method, and the results were analyzed for GO and KEGG enrichment. The results of RNA-seq were verified by qPCR analysis.
Results: The saffron was initially identified as authentic in the water test and 10 compounds were identified by Ultra Performance Liquid Chromatography (UPLC)- Mass Spectrometry (MS). The results of CCK-8 demonstrated that EES at concentrations above 640 μg/mL exerted a certain cytotoxic effect, and PC12 cells pretreated with EES (20, 40, and 80 μg/mL) significantly reversed the 500 μM CORT-induced cell death. RNA-seq analysis showed that EES regulated 246 differential genes, which were mainly enriched in the MAPK signaling pathway. Dusp5, Dusp6, Gadd45b, Gadd45G, and Pdgfc were further validated by qPCR. Experimental data showed that the results of qPCR were consistent with RNA-seq.
Conclusions: These findings provide an innovative understanding of the molecular mechanism of the protective effect of EES on PC12 cells at the molecular transcription level, and Dusp5, Dusp6, Gadd45b, Gadd45g, and Pdgfc may be potential novel targets for antidepressant treatment.

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