Increased Stress Hormone Levels Research Articles

Impact of tobacco smoke constituents on nicotine-seeking behavior in adolescent and adult male rats.

Given the rapid increase in teen vaping over recent years it is critical to understand mechanisms underlying addiction and relapse to tobacco use at this age. To evaluate the role of non-nicotine constituents in cigarette smoke, our lab has previously established a model of intravenous self-administration of aqueous cigarette smoke extract (CSE). We now compare the sensitivity of male adolescent and adult rats who have self-administered CSE or nicotine to reinstatement with the pharmacological stressor, yohimbine, with and without cues. Adolescents and adults, aged postnatal day (P) 34 and 84, were tested for the effect of yohimbine (0-2.5 mg/kg) on plasma corticosterone levels to establish a dose that was an effective stressor at both ages. Separate groups of animals were trained to lever press for food before beginning 1-hour drug self-administration sessions for nicotine or CSE (15 μg/kg/infusion nicotine content). Once stable responding was reached, drug was removed, and behavior extinguished. Drug-seeking behavior was reinstated with yohimbine, cues, or a combination of yohimbine and cues. Although adolescents and adults showed different dose-responses for yohimbine-induced corticosterone release, a dose of 2.5 mg/kg increased stress hormone levels at both ages. Whereas both ages displayed similar responding for CSE and nicotine, adolescents self-administered more CSE and nicotine as compared to adults. Cues and cues + stress reinstated responding to a greater extent in animals that had self-administered CSE, regardless of age. These findings suggest that non-nicotine tobacco smoke constituents influence later but not earlier stages of addiction in both adolescent and adult male rats.

Kinetics of lipid indicators in response to short- and long-duration whole-body, cold-water immersion

Cold exposure-induced secretion of stress hormones activates cold-defense responses and mobilizes substrates for increased energy demands to fuel thermogenesis. However, it is unclear whether acute cold exposure-induced stress hormone response kinetics affect circulating lipid parameter kinetics. Therefore, we aimed to investigate the 2-day kinetics of stress hormones (i.e., cortisol, epinephrine, and norepinephrine) and the lipid profile (i.e., total cholesterol [TC], high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides) in response to whole-body long- (intermittent 170 min; 170-CWI) or short-duration (10 min; 10-CWI) cold-water immersion (CWI; 14 °C water) in 17 healthy, young, adult men. Both CWI trials induced a marked release of the stress hormones, epinephrine, and norepinephrine, with higher concentrations detected after 170-CWI (p < 0.05) and a disrupted diurnal peak of cortisol lasting for a few hours. 170-CWI increased triglyceride levels from immediately after until 2 h after CWI, thereafter the concentration decreased at 4 h, 6 h, 1 day and 2 days after CWI (p < 0.05). Furthermore, the HDL-cholesterol level increased immediately after and at 6 h after 170-CWI (p < 0.05), while TC and LDL-cholesterol levels were not altered within 2 days. Lipid parameters were not affected within the 2 days after 10-CWI. Although both CWIs decreased deep body temperature and increased stress hormone levels for a few hours, only long-duration CWI induced changes in the circulating lipid profile within 2 days after CWI. This should be considered when discussing therapeutic protocols to improve circulating lipid profiles and ameliorate diseases associated with such profiles.

The key to superior memory encoding under stress: the relationship between cortisol response and mnemonic discrimination.

Some previous studies have shown that increased stress hormone levels have beneficial effects on memory encoding; however, there is no clear consensus on which encoding-related processes are affected by stress hormones. In the present study, we investigated the relationship between interindividual differences in neuroendocrine response to acute stress and interference resolution (i.e., mnemonic discrimination). Participants were healthy young adults who were exposed to physical and psychological stressors (Socially Evaluated Cold Pressor Test). Then participants completed the modified version of the Mnemonic Similarity Task. Specifically, they were presented with photographs of emotionally arousing (negative and positive) and nonarousing (neutral) scenes followed by a recognition memory test where they saw a mixture of old and new stimuli. Crucially, participants were also presented with critical lure items, that is, visually similar stimuli to ones presented at encoding. We found that participants who had higher cortisol response to the stressors were better in discriminating between the studied items and their visually similar lures. This effect was present for the arousing and nonarousing materials as well. These findings suggest that increased hormonal response to acute stress has a beneficial impact on the formation of distinct, nonoverlapping, unique memory representations, and consequently, on episodic memory encoding processes.

Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer

Excess mental stress may harm health, and even accelerate cancer initiation and progression. One fourth of breast cancer patients suffer mental stress including anxiety, sadness, or depression, which negatively affect prognosis and survival. However, the regulatory mechanism is yet to be determined. Herein, we applied unpredictable stress stimuli to the breast tumor-bearing mice to establish a xenograft model of breast cancer suffering mental stress, followed by behavioral tests, tumor growth tracking, immune analysis, miRNA screening, and tumor cell proliferation analysis as well. As a result, increased stress hormone levels in serum, decreased percentage of T and NK cells in both blood and tumor samples and accelerated tumor growth in vivo were observed in the mice exposed to mental stress. Promoted cell proliferation was observed in both primary tumor cells derived from the stressed mice and 4T1 breast cancer cells treated with stress hormone corticosterone. In addition, a subset of miRNAs including miR-326, 346, 493, 595, 615, and 665 were identified through a miRNA screening with downregulation in tumors of the stressed mice. CCND1 was identified as a common target gene of miR-346 and miR-493, the top two most significantly downregulated miRNAs by stress exposure. The stress-miRNA-CCND1 signaling regulation of the tumor cell proliferation was further validated in 4T1 cells treated with corticosterone in vitro. GO terms and KEGG pathways analyses on the target genes of miR-346 and miR-493 revealed their involvement in the regulation of human cancer and neuron system, indicating the importance of non-coding genome in mediating the mental stress-induced cancer regulation. In conclusion, this study not only explored immune and nonimmune mechanisms through which mental stress exposure contributes to tumor growth in breast cancer, but also suggested a new therapeutic strategy for cancer patients suffering mental stress.

Acupuncture Alleviates Anxiety and 22-kHz Ultrasonic Vocalizations in Rats Subjected to Repeated Alcohol Administration by Modulating the Brain-Derived Neurotrophic Factor/Corticotropin-Releasing Hormone Signaling Pathway.

The Shenmen point (acupuncture point heart 7: HT7), located in the heart meridian, is frequently used to treat mental disorders, including drug addiction, anxiety, and depression. This study aimed to determine how HT7 regulates anxiety and negative emotions caused by repeated alcohol administration, focusing on the amygdala and paraventricular nucleus (PVN). Repeated administration of alcohol (ETOH; 2 g/kg, i.p. injection, 16% v/v) for 14 days increased the corticosterone (CORT) levels, and HT7 stimulation reduced the plasma CORT levels. HT7 stimulation mitigated anxiety-like behaviors and reduced 22-kHz ultrasonic vocalizations in rats receiving repeated ETOH injections. HT7 stimulation increased the amygdala expression of mature brain-derived neurotropic factor (mBDNF) and phosphorylated tropomyosin receptor kinase B (pTrkB) and decreased the PVN corticotropin-releasing hormone (CRH) expression. Amygdala microinjections of the TrkB antagonist ANA-12 (0.1 pmol/1 μL) reversed the increase in PVN CRH levels. The reduced PVN CRH levels were regulated by CRH-expressing neurons in the amygdala, and the increased amygdala CRH levels were affected by the HT7-stimulation induced increases in mBDNF. HT7 stimulation alleviates increased stress hormone levels and mitigates anxiety and negative emotions caused by repeated ETOH administration. These results provide scientific support for the clinical use of acupuncture to treat various alcoholism-induced diseases.

Physiological and Behavioral Responses to Vocalization Playback in Mice.

In mice, the caller’s production of social vocalizations has been extensively studied but the effect of these vocalizations on the listener is less understood, with playback studies to date utilizing one vocalization category or listeners of one sex. This study examines how several categories of mouse vocalizations affect listeners of both sexes to better understand the communicative functions of these vocal categories. We examined physiological and behavioral responses of male and female CBA/CaJ mice to playback of four social vocalization categories: ultrasonic vocalizations (USVs), low-frequency harmonic calls, mid-frequency vocalizations, and noisy calls. Based on the conditions under which these calls are emitted, we hypothesized that playback of these vocal categories would have differential effects on the listeners. In females, playback of all four vocalization categories increased stress hormone levels (corticosterone), but only the non-USV categories increased corticosterone in males. The magnitude of corticosterone increase in non-USV trials was greater in females than in males. In open field tests, all four vocal categories decreased central ambulation in males and females, indicating an increase in anxiety-related behavior. Further, we found that the proportions of USVs emitted by subjects, but not their overall calling rates, were affected by playback of some vocal categories, suggesting that vocalization categories have different communication content. These results show that, even in the absence of behavioral and acoustic contextual features, each vocal category evokes physiological and behavioral responses in mice, with some differences in responses as a function of the listener’s sex and playback signal. These findings suggest that at least some of the vocal categories have distinct communicative functions.

Cognitive dysfunction in mice lacking proper glucocorticoid receptor dimerization

Stress is a major risk factor for depression and anxiety. One of the effects of stress is the (over-) activation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of stress hormones such as glucocorticoids (GCs). Chronically increased stress hormone levels have been shown to have detrimental effects on neuronal networks by inhibiting neurotrophic processes particularly in the hippocampus proper. Centrally, GCs modulate metabolic as well as behavioural processes by activating two classes of corticoid receptors, high-affinity mineralocorticoid receptors (MR) and low-affinity glucocorticoid receptors (GR). Upon activation, GR can modulate gene transcription either as a monomeric protein, or as a dimer interacting directly with DNA. GR can also modulate cellular processes via non-genomic mechanisms, for example via a GPCR-protein interaction. We evaluated the behavioral phenotype in mice with a targeted mutation in the GR in a FVB/NJ background. In GRdim/dim mice, GR proteins form poor homodimers, while the GR monomer remains intact. We evaluated the effect of poor GR dimerization on hippocampus-dependent cognition as well as on exploration and emotional behavior under baseline and chronically increased stress hormone levels. We found that GRdim/dim mice did not behave differently from GRwt/wt littermates under baseline conditions. However, after chronic elevation of stress hormone levels, GRdim/dim mice displayed a significant impairment in hippocampus-dependent memory compared to GRwt/wt mice, which correlated with differential expression of hippocampal Bdnf/TrkB and Fkbp5.

Environmental Noise-Induced Effects on Stress Hormones, Oxidative Stress, and Vascular Dysfunction: Key Factors in the Relationship between Cerebrocardiovascular and Psychological Disorders.

The role of noise as an environmental pollutant and its adverse effects on health are being increasingly recognized. Beyond its direct effects on the auditory system (e.g., hearing loss and tinnitus induced by exposure to high levels of noise), chronic low-level noise exposure causes mental stress associated with known cardiovascular complications. According to recent estimates of the World Health Organization, exposure to traffic noise is responsible for a loss of more than 1.5 million healthy life years per year in Western Europe alone, a major part being related to annoyance, cognitive impairment, and sleep disturbance. Underlying mechanisms of noise-induced mental stress are centered on increased stress hormone levels, blood pressure, and heart rate, which in turn favor the development of cerebrocardiovascular disease such as stroke, arterial hypertension, ischemic heart disease, and myocardial infarction. Furthermore, traffic noise exposure is also associated with mental health symptoms and psychological disorders such as depression and anxiety, which further increase maladaptive coping mechanisms (e.g., alcohol and tobacco use). From a molecular point of view, experimental studies suggest that traffic noise exposure can increase stress hormone levels, thereby triggering inflammatory and oxidative stress pathways by activation of the nicotinamide adenine dinucleotide phosphate oxidase, uncoupling of endothelial/neuronal nitric oxide synthase inducing endothelial and neuronal dysfunction. This review elucidates the mechanisms underlying the relationship between noise exposure and cerebrocardiovascular and psychological disorders, focusing on mental stress signaling pathways including activation of the autonomous nervous system and endocrine signaling and its association with inflammation, oxidative stress, and vascular dysfunction.

Towards optimized anesthesia protocols for stereotactic surgery in rats: Analgesic, stress and general health effects of injectable anesthetics. A comparison of a recommended complete reversal anesthesia with traditional chloral hydrate monoanesthesia

Although injectable anesthetics are still widely used in laboratory rodents, scientific data concerning pain and distress during and after stereotactic surgery are rare. However, optimal anesthesia protocols have a high impact on the quality of the derived data. We therefore investigated the suitability of recommended injectable anesthesia with a traditionally used monoanesthesia for stereotactic surgery in view of optimization and refinement in rats. The influence of the recommended complete reversal anesthesia (MMF; 0.15mg/kg medetomidine, 2mg/kg midazolam, 0.005mg/kg fentanyl; i.m.) with or without reversal and of chloral hydrate (430mg/kg, 3.6%, i.p.) on various physiological, biochemical and behavioral parameters (before, during, after surgery) was analyzed. Isoflurane was also included in stress parameter analysis. In all groups, depth of anesthesia was sufficient for stereotactic surgery with no animal losses. MMF caused transient exophthalmos, myositis at the injection site and increased early postoperative pain scores. Reversal induced agitation, restlessness and hypothermia. Even the low concentrated chloral hydrate led to peritonitis and multifocal liver necrosis, corresponding to increased stress hormone levels and loss in body weight. Increased stress response was also exerted by isoflurane anesthesia. Pronounced systemic toxicity of chloral hydrate strongly questions its further use in rodent anesthesia. In view of undesired effects of MMF and isoflurane, thorough consideration of anesthesia protocols for particular research projects is indispensable. Reversal should be restricted to emergency situations. Our data support further refinement of the current protocols and the importance of sham operated controls.

Children’s hair cortisol as a biomarker of stress at school entry

Quantification of cortisol in scalp hair seems a promising measurement for long-term cortisol levels, and thereby a biomarker for stress. We examined hair cortisol concentrations (HCC) in children when first entering elementary school. Participants were 42 children (45% boys) with a mean age of 4.2 years (SD = 0.42 months). Hair samples (≥5 cm) were collected 2 months after school entry. Hair analysis was conducted using two 2-cm long segments, reflecting the first 2 months of school attendance (the scalp-near segment) and 2 months prior to school entry. HCC were higher after school entry than before, especially for fearful children. Alterations in HCC were not moderated by experience in group daycare before school entry. Thus, HCC suggest that starting elementary school is accompanied by increased stress hormone levels in young (in particular fearful) children.

Serotonin 2C receptor antagonism ameliorates novelty-induced hypophagia in aged mice

This study was conducted to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) 2C receptor (5-HT2CR) signaling during novelty-induced hypophagia in aged mice. Male C57BL/6J mice [6-week-old (young) and 79-80-week-old (aged) mice] were exposed to a novel environment, and its effects on feeding behavior, stress hormones, and appetite-related factors were examined. Exposure of aged mice to a novel environment suppressed food intake and increased corticosterone secretion. These responses were marked compared with those in young mice. The expression in hypothalamic corticotropin-releasing factor (CRF), pituitary CRF1R and proopiomelanocortin mRNA in aged mice exposed to a novel environment was increased or tended to increase, compared to control mice. 5-HT2CR antagonist, SB242084 or rikkunshito administration attenuated the decrease in food intake and increased stress hormone levels in aged mice exposed to the environmental change. The 5-HT2CR mRNA expression in paraventricular nucleus was significantly enhanced, when aged mice was exposure to the novel environment. Thus, novelty-induced hypophagia in aged mice resulted, at least in part, from up-regulated hypothalamic 5-HT2CR function. In conclusion, 5-HT2CR signaling enhancement and the subsequent activation of the CRF neuron were involved in novelty-induced hypophagia in aged mice, and the 5-HT2CR antagonists offer a promising therapeutic option for depression.

Adrenocortical and Immune Responses Following Short- and Long-Duration Spaceflight

Short-term spaceflight is associated with significant but reversible immunological alterations. However, little information exists on the effects of long-duration spaceflight on neuroimmune responses. We collected multiple pre- and postflight samples from Shuttle and International Space Station (ISS) crewmembers in order to compare adrenocortical and immune responses between short- (approximately 11 d) and long-duration (approximately 180 d) spaceflight. In Shuttle crewmembers, increased stress hormone levels and altered leukocyte subsets were observed prior to launch and at landing. Additionally, typical stress-induced shifts in leukocyte and lymphocyte subsets, as well as the percentage of T-cells capable of producing intracellular IFN-gamma were also decreased just before launch and immediately after landing. Plasma IL-10 levels were increased before launch but not postflight. No preflight changes occurred in ISS crewmembers, but long-duration crewmembers exhibited significantly greater spikes in both plasma and urinary cortisol at landing as compared to Shuttle crewmembers. The percentage of T-cells capable of producing intracellular IFN-gamma was decreased in ISS crewmembers. Plasma IL-10 was increased postflight. Unexpectedly, stress-induced shifts in lymphocyte subpopulations were absent after long-duration flights despite significantly increased stress hormones at landing. Our results demonstrate significant differences in neuroimmune responses between astronauts flying on short-duration Shuttle missions versus long-duration ISS missions, and they agree with prior studies demonstrating the importance of mission duration in the magnitude of these changes.

Winter tourism increases stress hormone levels in the Capercaillie Tetrao urogallus

Montane and alpine habitats in Europe remained relatively undisturbed until the beginning of the last century. Today, outdoor recreation activities are a major economic factor in alpine regions. Many tourism areas coincide with winter habitats of shy and endangered species. The Western Capercaillie Tetrao urogallus has suffered from rapid population declines during recent decades over much of its range. In central Europe, many Capercaillie are exposed to intensive human recreation activities in their habitats, which may contribute to this decline. However, little is known about their susceptibility to human recreation activities. This study assessed whether human recreation in winter evokes physiological stress responses in several populations of Capercaillie. During two winters, we sampled 1130 Capercaillie droppings in Germany and Switzerland of populations at various distances from winter recreation activities and measured concentrations of faecal corticosterone metabolites. Capercaillie in relatively dense and homogeneous mountain forests dominated by Norway Spruce Picea abies showed markedly increased stress hormone levels closer to locations with winter recreation activity. However, this physiological response to human recreation was not detectable in forests dominated by various pine species and a heterogeneous structure. Capercaillie may be particularly sensitive to recreation because any factor affecting their fine‐tuned physiological and behavioural adaptations to survive under harsh winter conditions may lead to harmful fitness costs.

Diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is a complex and potentially fatal metabolic disorder in patients with diabetes mellitus. An understanding of the pathophysiology of DKA is essential in order to optimize patient management. A combination of insulin deficiency, increased stress hormone levels, and volume depletion account for the laboratory abnormalities and clinical signs observed in these patients. Successful therapy depends upon correction of hyperglycemia, dehydration, and electrolyte and blood gas abnormalities.