Study of Metabolomic Markers of β-Blocker Neurotoxicity Using Zebrafish as a Model Organism.
Using zebrafish (Danio rerio) as a model organism, we studied metabolomic markers of β-blocker neurotoxicity (propranolol, metoprolol, bisoprolol) and the relationships between neurotransmitter disturbances (dopamine, epinephrine, choline, cortisol) and their effects. Propranolol produced the most pronounced changes: significant increases in cortisol and epinephrine and decreases in dopamine and serotonin levels. Metoprolol caused a moderate increase in cortisol while elevating serotonin, suggesting a more balanced pharmacological profile. Bisoprolol had virtually no effect on cortisol or monoamine levels but increased the concentrations of choline, glycine, and glutamate. Differences in neurometabolic effects of β-blockers were identified: propranolol demonstrated a strong neurotoxic potential, consistent with its depressive side effects in humans; metoprolol showed an intermediate effect; while bisoprolol did not affect CNS. Zebrafish exhibited high sensitivity to neurochemical shifts, making this model valuable for preclinical drug neurotoxicity assessment.
- Research Article
10
- 10.1002/smi.2469
- Oct 22, 2012
- Stress and Health
Human perception of stress includes an automatic pathway that processes subliminal presented stimuli below the threshold of conscious awareness. Subliminal stimuli can therefore activate the physiologic stress system. Unconscious emotional signals were shown to significantly moderate reactions and responses to subsequent stimuli, an effect called 'priming'. We hypothesized that subliminal presentation of a fearful signal during the Stroop task compared with an emotionally neutral one will prime stress reactivity in a subsequently applied psychosocial stress task, thereby yielding a significant increase in salivary cortisol. Half of 36 participants were repeatedly presented either a fearful face or a neutral one. After this, all underwent a psychosocial stress task. The fearful group showed a significant increase in cortisol levels (p = 0.022). This change was not affected by sex, age and body mass index, and it also did not change when taking resting cortisol levels into account. Post-hoc analyses showed that the increase in cortisol in the fearful group started immediately after the psychosocial stress test. Hence, subliminal exposure to a fearful signal in combination with the Stroop and followed by a psychosocial stress test leads to an increase in stress reactivity.
- Research Article
11
- 10.1038/sj.jp.7211127
- May 20, 2004
- Journal of Perinatology
To compare the effects of in vivo mifepristone with placebo on plasma corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol levels concentrations in term human pregnancies. In all, 24 women participating in a randomized controlled trial of mifepristone for preinduction cervical ripening were enrolled in this ancillary study. Participants with uncomplicated singleton pregnancies beyond 41 weeks gestation and undilated, uneffaced cervices were randomized to either placebo or mifepristone 200 mg orally and observed for 24 hours prior to receiving either intravaginal misoprostol and/or intravenous oxytocin. Blood samples were obtained before medication administration, 3 and 6 hours later, and then every 6 hours until delivery. Plasma hormone levels were measured by radioimmunoassay. Basal levels of CRH, ACTH, and cortisol were similar in the placebo (n=13) and mifepristone groups (n=11). Compared to placebo treatment, exposure to mifepristone resulted in significant elevation of plasma cortisol within 18 hours. Plasma CRH and ACTH were unaffected. Progression of labor was associated with significant increases in cortisol in both groups, while CRH and ACTH levels were not altered. Compared to basal levels within each group, plasma cortisol at delivery was significantly elevated within both the mifepristone (156.8+/-17.7 vs 332.6+/-48.5 ng/ml, p=0.008) and the placebo (166.6+/-34.3 vs 342.4+/-46.4 ng/ml, p=0.003) groups. However, plasma CRH, ACTH, and cortisol levels at delivery did not differ between the groups. Mifepristone exposure and induced labor were associated with significant increases in plasma cortisol without alterations of systemic CRH or ACTH levels.
- Research Article
1
- 10.7586/jkbns.24.011
- Aug 20, 2024
- Journal of Korean Biological Nursing Science
Purpose: This study investigated changes in psychological and physiological indices in cancer survivors who participated in a forest therapy camp in Korea.Methods: A total of 37 cancer survivors (19 and 18 in the experimental and control groups, respectively) participated in this study. Over a 2-night and 3-day period, the participants in the experimental group took part in a forest therapy camp that included activities such as gymnastics, walking, five-senses experiences, and meditation. Both groups completed self-report questionnaires that measured their stress levels and profile of mood states, both before and after the forest therapy camp. Blood samples were collected to measure the levels of cortisol, serotonin, and natural killer (NK) cells.Results: After the forest therapy camp, the experimental group exhibited reduced stress levels (p = .031) and a significant improvement in total mood disturbance (p = .047) when compared with the control group. The level of serotonin also significantly increased (p < .001). However, in contrast to the prediction, a significant increase in cortisol was noted in the experimental group relative to the control group (p = .016). Moreover, no significant difference in NK cells was noted between the two groups.Conclusion: Forest therapy can be easily applied to cancer survivors. The positive psychological effects of the forest therapy camp were confirmed by improvements in stress and mood states and the increased level of serotonin in forest therapy camp participants. However, there is a need for a follow-up evaluation of cortisol and NK cells due to the absence of significant between-group differences.
- Research Article
28
- 10.1016/j.cca.2009.06.032
- Jul 1, 2009
- Clinica chimica acta; international journal of clinical chemistry
HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: A two-year follow-up study
- Research Article
216
- 10.1016/s0306-4522(97)00565-4
- Feb 1, 1998
- Neuroscience
Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release
- Research Article
19
- 10.1002/ame2.12215
- Feb 16, 2022
- Animal Models and Experimental Medicine
BackgroundTDCPP is one of the major chemical of organophosphate flame retardants (OPFRs) that has been detected ubiquitously in both the environment and biota. Previously we observed that it influenced the concentrations of sex and thyroid hormones in a sex‐dependent pattern, leading to reproductive impairments after short‐term exposure in zebrafish. Here we investigate the consequences of longer‐term exposure to TDCPP on the hypothalamic‐pituitary‐gonad (HPG), hypothalamic‐pituitary‐interrenal (HPI), and hypothalamic‐pituitary‐thyroid (HPT) axes of zebrafish (Danio rerio).MethodsA 120‐day exposure test to 0.005, 0.05 and 0.5 mg/L TDCPP was initiated with fertilized eggs. Sex steroid hormones in the treated fishes were measured and transcriptional changes were analyzed.ResultsIn female fish, exposure to TDCPP resulted in increases in plasma cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β‐estradiol (E2), cortisol, thyroxine (T4), and triiodothyronine (T3). Transcription of most target genes along HPG, HPI and HPT axes were increased by the exposure. While in male fish the exposure led to decreases in cortisol, FSH, LH, T4, T3, testosterone (T), and 11‐ketotestosterone (11‐KT). Transcription of genes along HPG, HPI and HPT axes, especially steroidogenic genes, were inhibited in male zebrafish. While, E2/T or E2/11‐KT ratio was increased in both female and females. The sex‐dependent changes in hormones might be due to differential responses to TDCPP induced stresses. An increase in cortisol level coincided with increases in E2 and THs in female fish, while in males decreases in cortisol as well as T, 11‐KT and THs were observed. Long‐term exposure to TDCPP at very low (μg/L) concentrations could disrupt hormone balances in a sex dependent way.ConclusionThis study revealed that TDCPP could affect endocrine axes – HPG, HPI and HPT – in zebrafish, and impair zebrafish development.
- Research Article
27
- 10.1093/biolreprod/52.monograph_series1.53
- Jan 1, 1995
- Biology of Reproduction
The effects of in utero exposure to the fescue endophyte Acremonium coenophialum on neonatal Cortisol, thyroid hormone, and progestagen concentrations were examined. Blood samples were collected at birth from 12 mares and foals exposed to the fescue endophyte A. coenophialum (E +; mean gestation, 358 days) and 6 mares and foals grazing endophyte-free (E −) fescue (mean gestation, 334 days). The plasma was assayed for tri-iodothyronine (T3), thyroxine (T4), reverse T3 (rT3), Cortisol, ACTH, and total progestagens by standard RIA. The maternal total progestagen concentration was significantly lower (p < 0.01; 4.7 ng/ml) in mares grazing E + fescue compared to mares grazing E − fescue (22.4 ng/ml). In the foals exposed in utero to endophyte, total progestagens, Cortisol, and T3 concentrations were significantly lower (p < 0.01; 6.7 ± 2.2 vs. 42.4 ± 8.5 ng/ml progestagens; 145.3 ± 23.1 vs. 360.0 ± 21.4 ng/ml T3; and 4.1 ± 2.1 vs. 59.5 ± 6.1 ng/ml Cortisol) than corresponding concentrations in foals not exposed to endophyte. ACTH concentrations in foals that died acutely after delivery were significantly lower at birth than values in foals that survived (37.6 ± 16.47 vs. 291.4 ± 69.8 ng/ml). Umbilical vein progestagen concentrations did not differ between treatment groups (19.7 ± 3.2 vs. 18.3 ± 2.7 ng/ml). In foals that survived the natal period, there was a significant increase in Cortisol, T3, and progestagens from birth to 12 h of age. In foals that succumbed within the first 24 h, no increase in progestagens, T3, or Cortisol was noted. These results demonstrate that exposure of pregnant mares to A. coenophialum-infected tall fescue results in altered neonatal adrenocortical and thyroid hormone production. Placental steroidogenesis as evidenced by umbilical vein progestagen concentrations appears unaffected. Therefore, we suggest that prolonged gestation and fetal dysmaturity in fescue toxicoses results from abnormal adrenal and thyroid hormone production by the late-term fetus.
- Research Article
- 10.1016/j.cpnec.2021.100043
- Mar 3, 2021
- Comprehensive Psychoneuroendocrinology
Differential stress response to psychological and physical stressors in children using spatial versus response-dependent navigation strategies
- Abstract
- 10.1016/j.ymgme.2019.11.197
- Jan 31, 2020
- Molecular Genetics and Metabolism
Neurodevelopmental outcomes in patients with mucopolysaccharidosis type I (MPS I)
- Research Article
- 10.33295/1992-576x-2024-6-21
- Jan 1, 2024
- SUCHASNA STOMATOLOHIYA
Actuality. The prevalence of periodontal tissue diseases among the adult population of working age from 35 to 55 years is quite high. It has no tendency to decrease, which makes this problem extremely urgent. Psychoemotional attitude to pain, negative experience of previous treatment, and the patientfs dental anxiety prevent visits to the clinic for a long time, which exacerbates inflammation and complicates the treatment of patients with generalized periodontitis with manifestations of anxiety. Purpose. Analyze the level of cortisol in oral fluid in patients with generalized periodontitis, with manifestations of anxiety before and after treatment. Research materials and methods. A study of the cortisol level was conducted in 157 patients with generalized periodontitis with manifestations of anxiety, aged 35.55 years, and the gender composition of patients.men (28.7%) and women (71.3%). Patients are divided into three groups. The examination was carried out before and after treatment. Research results. It was found that the level of cortisol in the oral fluid increases in patients with generalized periodontitis in those groups with an increased or high level of anxiety. Before treatment, a significant increase in cortisol in the oral fluid was found in groups HP-T1 with a moderate level of anxiety and in groups HP-T2 with a high level of anxiety found a significant increase in cortisol in the oral fluid. After the medical and preventive measures, the cortisol levels decreased. In particular, in the 35.44 age group, at 10:00 a.m., the cortisol level decreased from 3.02 } 1.87 ng/ml to 2.52 } 1.57 ng/ml. According to Fisherfs test, it is significantly correlated (p . 0.05) with the group results. In the age group of 45.55 years old treatment, the cortisol level was 3.71 } 1.9 ng/ml. After treatment, it decreased to 2.77 } 1.5 ng/ml, which also correlates with the results by group (p . 0.05) according to Fisherfs test. The indicators did not change significantly in the control group. Thus, an increase in the level of inflammation of the periodontal tissues in generalized periodontitis and an increase in the level of anxiety increases the cortisol level in saliva. After the treatment, the results in the groups significantly changed, which was statistically significantly (p < 0.05) different from the indicators of the control group. Conclusions. Oral fluid cortisol testing is a convenient, noninvasive method for assessing anxiety levels in patients. Comprehensive treatment and corrective and preventive measures for patients with generalized periodontitis who manifested anxiety brought the cortisol level closer to the reference values. Keywords: generalized periodontitis, dental anxiety, stress, cortisone, treatment, prevention, correction.
- Research Article
2
- 10.4172/2161-1017.1000159
- Jan 1, 2016
- Endocrinology & Metabolic Syndrome
Background: Cold exposure is a permanent part of human life. Response to cold varies according to different factors and individual differences. The main factors potentially differentiating thermoregulation in men and women are the properties of female physiology, anthropometric characteristics, body composition, social behavior and physical working capacity. Aim of the study: Detecting the effect of short term cold exposure or cold season on body weight, food consumption, and levels of TSH, T3 , T4 , insulin, glucagon, adrenaline, cortisol, testosterone, progesterone and estrogen. Material and methods: This study was carried out on 96 adult albino rats of local strain, half of them were males and the other half were females. The animals were divided equally into two control groups (males and females), and four experimental groups (two males and two females). Each group was divided into two equal sub-groups (one for morning experiment where blood samples were collected at 7:00 a.m to 8:00 a.m., and one for night experiment where blood samples were collected at 700 p.m to 8:00 p.m.). Blood samples were taken at the end of experimental period (7 days) for determination of TSH, T3 , T4 , insulin, glucagon, adrenaline, cortisol, testosterone, and progesterone and estrogen levels. Results: Exposure of the body to cold produced the physiological responses according to the degree of cooling. The more severe the exposure to cold, the more marked were the effects that can be observed in body heat balance. Thyroid hormones increased through release of hypothalamus to TRH which led to release of TSH from the pituitary gland. Cortisol increased through stimulation of HPA axis. Adrenaline increased through stimulation of sympathetic nervous system and led to vasoconstriction and increased the release of fatty acids from adipose tissue to be used as energy substrates for heat production. Increased activity of the sympathetic nervous system during cold exposure led to decreased insulin secretion to increase blood glucose level which was used as a fuel for heat production. Activation of HPA was associated with increased progesterone hormone which has a role in thermogenesis. The increased needs for heat production in cold situations to keep body temperature constant led to increased food consumption, and the body weight showed no changes. This was because energy intake was used for heat production. Conclusion: Exposure to 4°C for 60 minutes for seven days cause significant increase in cortisol, adrenaline, estrogen, progesterone, insulin, T3 and TSH, while testosterone significantly decreased. Also, exposure to 15-17°C for seven days caused significant increase in cortisol, adrenaline, estrogen and progesterone, while testosterone hormone significantly decreased. No significant changes occurred in T4 and glucagon.
- Research Article
3
- 10.1016/j.apunts.2019.11.001
- Oct 1, 2019
- Apunts. Medicina de l'Esport
Resistance exercise on two consecutive days induces cortisol, CK, IgA responses in active young males
- Abstract
- 10.1016/0168-0102(85)90275-5
- Jan 1, 1985
- Neuroscience Research
In vivo output of neurotransmitters and metabolite from the lateral ventricle in freely-moving rats
- Abstract
- 10.1016/j.psyneuen.2023.106207
- Jun 15, 2023
- Psychoneuroendocrinology
Does a laboratory-based CO2 challenge induce a hypothalamic-pituitary-adrenal (HPA) axis stress response in healthy adults?
- Research Article
111
- 10.1016/s0306-4522(99)00211-0
- Aug 1, 1999
- Neuroscience
Buspirone modulates basal and fluoxetine-stimulated dialysate levels of dopamine, noradrenaline and serotonin in the frontal cortex of freely moving rats: activation of serotonin 1A receptors and blockade of α 2-adrenergic receptors underlie its actions