scholarly journals Severe hypoxia exposure inhibits larval brain development but does not affect the capacity to mount a cortisol stress response in zebrafish

2021 ◽  
Author(s):  
Kristina V. Mikloska ◽  
Zoe A. Zrini ◽  
Nicholas J. Bernier
Keyword(s):  
Stress Response ◽  
Brain Development ◽  
Hypoxia Tolerance ◽  
Severe Hypoxia ◽  
Whole Body ◽  
Hypoxic Exposure ◽  
Larval Brain ◽  
Fish Nursery ◽  
Hypoxia Exposure ◽  
The Impact

Fish nursery habitats are increasingly hypoxic and the brain is recognized as highly hypoxia-sensitive, yet there is a lack of information on the effects of hypoxia on the development and function of the larval fish brain. Here, we tested the hypothesis that by inhibiting brain development, larval exposure to severe hypoxia has persistent functional effects on the cortisol stress response in zebrafish (Danio rerio). Exposing 5 days post-fertilization (dpf) larvae to 10% dissolved O2 (DO) for 16 h only marginally reduced survival, but it decreased forebrain neural proliferation by 55%, and reduced the expression of neurod1, gfap, and mbpa, markers of determined neurons, glia, and oligodendrocytes, respectively. The 5 dpf hypoxic exposure also elicited transient increases in whole body cortisol and in crf, uts1, and hsd20b2 expression, key regulators of the endocrine stress response. Hypoxia exposure at 5 dpf also inhibited the cortisol stress response to hypoxia in 10 dpf larvae and increased hypoxia tolerance. However, 10% DO exposure at 5 dpf for 16h did not affect the cortisol stress response to a novel stressor in 10 dpf larvae or the cortisol stress response to hypoxia in adult fish. Therefore, while larval exposure to severe hypoxia can inhibit brain development, it also increases hypoxia tolerance. These effects may transiently reduce the impact of hypoxia on the cortisol stress response but not its functional capacity to respond to novel stressors. We conclude that the larval cortisol stress response in zebrafish has a high capacity to cope with severe hypoxia-induced neurogenic impairment.

The evolutionary and physiological significance of the Hif pathway in teleost fishes

2021 ◽  
Vol 224 (18) ◽  
Author(s):  
Milica Mandic ◽  
William Joyce ◽  
Steve F. Perry
Keyword(s):  
Hypoxia Inducible Factor ◽  
Duplication Event ◽  
Hypoxia Tolerance ◽  
Evolutionary Significance ◽  
Hypoxic Exposure ◽  
Cardiorespiratory System ◽  
Genome Duplication Event ◽  
Hypoxic Response ◽  
Hif Pathway ◽  
The Impact

ABSTRACT The hypoxia-inducible factor (HIF) pathway is a key regulator of cellular O2 homeostasis and an important orchestrator of the physiological responses to hypoxia (low O2) in vertebrates. Fish can be exposed to significant and frequent changes in environmental O2, and increases in Hif-α (the hypoxia-sensitive subunit of the transcription factor Hif) have been documented in a number of species as a result of a decrease in O2. Here, we discuss the impact of the Hif pathway on the hypoxic response and the contribution to hypoxia tolerance, particularly in fishes of the cyprinid lineage, which includes the zebrafish (Danio rerio). The cyprinids are of specific interest because, unlike in most other fishes, duplicated paralogs of the Hif-α isoforms arising from a teleost-specific genome duplication event have been retained. Positive selection has acted on the duplicated paralogs of the Hif-α isoforms in some cyprinid sub-families, pointing to adaptive evolutionary change in the paralogs. Thus, cyprinids are valuable models for exploring the evolutionary significance and physiological impact of the Hif pathway on the hypoxic response. Knockout in zebrafish of either paralog of Hif-1α greatly reduces hypoxia tolerance, indicating the importance of both paralogs to the hypoxic response. Here, with an emphasis on the cardiorespiratory system, we focus on the role of Hif-1α in the hypoxic ventilatory response and the regulation of cardiac function. We explore the effects of the duration of the hypoxic exposure (acute, sustained or intermittent) on the impact of Hif-1α on cardiorespiratory function and compare relevant data with those from mammalian systems.

THE IMPACT OF HORSERADISH ROOTS ($ARMORACIA$ $RUSTICANA$) ON THE FUNCTIONAL STATE OF RAT BODY IN ACUTE HYPOXIA

2020 ◽  
Vol 54 (3 (253)) ◽  
pp. 223-228
Author(s):  
M.A. Karapetyan ◽  
S.G. Sahakyan ◽  
N.Yu. Adamyan
Keyword(s):  
Functional State ◽  
Oxygen Deficiency ◽  
Acute Hypoxia ◽  
Food Supplement ◽  
Hypoxic Exposure ◽  
Statistical Parameters ◽  
Armoracia Rusticana ◽  
Hypoxia Exposure ◽  
Hardware Complex ◽  
The Impact

Using the “Bioscope” hardware complex, it was shown that an oxygen deficiency leads to certain changes in the statistical parameters of the integrative state of animals both during and after hypoxia exposure. However, after 10 days of using horseradish roots (Armoracia rusticana) as an antihypoxic food supplement, in contrast to the control, significant changes in the recorded signal are observed both during and after hypoxic exposure. These changes indicate the facilitating effect of horseradish roots in conditions of oxygen deficiency.

Effects of live high, train low hypoxic exposure on lactate metabolism in trained humans

2004 ◽  
Vol 96 (2) ◽  
pp. 517-525 ◽  
Author(s):  
Sally A. Clark ◽  
Robert J. Aughey ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Nathan E. Townsend ◽  
...  
Keyword(s):  
Ph Regulation ◽  
Whole Body ◽  
Hypoxic Exposure ◽  
Protein Abundance ◽  
Lactate Metabolism ◽  
Hypoxia Exposure ◽  
Before And After ◽  
Resting Muscle

We determined the effect of 20 nights of live high, train low (LHTL) hypoxic exposure on lactate kinetics, monocarboxylate lactate transporter proteins (MCT1 and MCT4), and muscle in vitro buffering capacity (βm) in 29 well-trained cyclists and triathletes. Subjects were divided into one of three groups: 20 consecutive nights of hypoxic exposure (LHTLc), 20 nights of intermittent hypoxic exposure [four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia (LHTLi)], or control (Con). Rates of lactate appearance (Ra), disappearance (Rd), and oxidation (Rox) were determined from a primed, continuous infusion of l-[U-14C]lactic acid tracer during 90 min of steady-state exercise [60 min at 65% peak O2 uptake (V̇o2 peak) followed by 30 min at 85% V̇o2 peak]. A resting muscle biopsy was taken before and after 20 nights of LHTL for the determination of βm and MCT1 and MCT4 protein abundance. Ra during the first 60 min of exercise was not different between groups. During the last 25 min of exercise at 85% V̇o2 peak, Ra was higher compared with exercise at 65% of V̇o2 peak and was decreased in LHTLc ( P < 0.05) compared with the other groups. Rd followed a similar pattern to Ra. Although Rox was significantly increased during exercise at 85% compared with 65% of V̇o2 peak, there were no differences between the three groups or across trials. There was no effect of hypoxic exposure on βm or MCT1 and MCT4 protein abundance. We conclude that 20 consecutive nights of hypoxia exposure decreased whole body Ra during intense exercise in well-trained athletes. However, muscle markers of lactate metabolism and pH regulation were unchanged by the LHTL intervention.

A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Varvara Kanti ◽  
Lia Puder ◽  
Irina Jahnke ◽  
Philipp Maximilian Krabusch ◽  
Jan Kottner ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Skin Pigmentation ◽  
Gene Mutations ◽  
Continuous Treatment ◽  
Whole Body ◽  
Hair Color ◽  
Phase 2 ◽  
Loss Of Function ◽  
The Impact ◽  
Over Time

<b><i>Background and Objectives:</i></b> Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist <i>setmelanotide</i> in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with <i>setmelanotide,</i> changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. <b><i>Methods:</i></b> In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist <i>setmelanotide</i>. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. <b><i>Results:</i></b> We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of <i>setmelanotide</i> treatment. <b><i>Discussion:</i></b> <i>Setmelanotide</i> treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

scholarly journals The Impact of Nordic Walking on Bone Properties in Postmenopausal Women with Pre-Diabetes and Non-Alcohol Fatty Liver Disease

2021 ◽  
Vol 18 (14) ◽  
pp. 7570
Author(s):  
Xiaming Du ◽  
Chao Zhang ◽  
Xiangqi Zhang ◽  
Zhen Qi ◽  
Sulin Cheng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Postmenopausal Women ◽  
Fatty Liver Disease ◽  
Whole Body ◽  
Nordic Walking ◽  
Significant Group ◽  
Time Interaction ◽  
Bone Properties ◽  
The Impact

This study investigated the impact of Nordic walking on bone properties in postmenopausal women with pre-diabetes and non-alcohol fatty liver disease (NAFLD). A total of 63 eligible women randomly participated in the Nordic walking training (AEx, n = 33), or maintained their daily lifestyle (Con, n = 30) during intervention. Bone mineral content (BMC) and density (BMD) of whole body (WB), total femur (TF), femoral neck (FN), and lumbar spine (L2-4) were assessed by dual-energy X-ray absorptiometry. Serum osteocalcin, pentosidine, receptor activator of nuclear factor kappa-B ligand (RANKL) levels were analyzed by ELISA assay. After an 8.6-month intervention, the AEx group maintained their BMCTF, BMDTF, BMCL2−4, and BMDL2−4, and increased their BMCFN (p = 0.016), while the Con group decreased their BMCTF (p = 0.008), BMDTF (p = 0.001), and BMDL2−4 (p = 0.002). However, no significant group × time interaction was observed, except for BMDL2−4 (p = 0.013). Decreased pentosidine was correlated with increased BMCWB(r = −0.352, p = 0.019). The intervention has no significant effect on osteocalcin and RANKL. Changing of bone mass was associated with changing of pentosidine, but not with osteocalcin and RANKL. Our results suggest that Nordic walking is effective in preventing bone loss among postmenopausal women with pre-diabetes and NAFLD.

scholarly journals The Effect of Repeated Whole-Body Cryotherapy on Sirt1 and Sirt3 Concentrations and Oxidative Status in Older and Young Men Performing Different Levels of Physical Activity

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 37
Author(s):  
Gabriela Wojciak ◽  
Jadwiga Szymura ◽  
Zbigniew Szygula ◽  
Joanna Gradek ◽  
Magdalena Wiecek
Keyword(s):  
Physical Activity ◽  
Young Men ◽  
Oxidative Status ◽  
Whole Body ◽  
Stress Index ◽  
Blood Levels ◽  
Long Distance ◽  
Antioxidant Defence ◽  
Whole Body Cryotherapy ◽  
The Impact

Background: The activity of antioxidant enzymes and sirtuins (Sirt) decreases along with age, which is counteracted by aerobic training. Sirtuins increase antioxidant defence. Whole-body cryotherapy (WBC) increases total antioxidant capacity (TAC) in young men. The aim of our study was to assess the impact of 24 WBC treatments on the blood concentration of selected sirtuins and the level of antioxidant defence as well as oxidative stress index of training and non-training men depending on age. Methods: The study involved 40 males. In each group, there were 10 non-training older and young men (60 NTR and 20 NTR), and 10 older and young long-distance runners (60 TR, 20 TR). During an 8-week period, participants underwent 24 WBC treatments (3 min −130 °C), which were performed three times a week (Monday, Wednesday, Friday). The concentrations of Sirt1, Sirt3, TAC, total oxidative status and the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the blood were determined before 1 WBC and after 1 WBC, 12 WBC and 24 WBC. Results: After 1 WBC, the activity of GPx and the concentration of Sirt1 and TAC in 60 TR and TAC in 60 NTR increased. After 12 WBC, the level of Sirt1 in 20 NTR and SOD in 20 TR increased. After 24 WBC, the level of Sirt1 increased in 60 TR and in 20 NTR, Sirt3 in 60 TR and SOD in 20 TR. Conclusions: Cryogenic temperatures increase blood levels of Sirt1 and Sirt3 and systemic antioxidant defence in men, but the effect is dependent on age, level of performed physical activity and the number of applied treatments.

scholarly journals Weight Status and Visceral Adiposity Mediate the Relationship between Exclusive Breastfeeding Duration and Skin Carotenoids in Later Childhood

2021 ◽  
Author(s):  
Ruyu Liu ◽  
Caitlyn G Edwards ◽  
Corinne N Cannavale ◽  
Isabel R Flemming ◽  
Morgan R Chojnacki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Exclusive Breastfeeding ◽  
Weight Status ◽  
Mediating Effect ◽  
Physical Growth ◽  
Breastfeeding Duration ◽  
Whole Body ◽  
Controlled Clinical Trial ◽  
The Impact ◽  
The Relationship

Abstract Background Breastfeeding is associated with healthier weight and nutrient status in early life. However, the impact of breastfeeding on carotenoid status beyond infancy, and the influence of adiposity, is unknown. Objective The aim of the study was to retrospectively investigate the relationship between breastfeeding and carotenoid status, and the mediating effect of weight status and adiposity on this relationship among school-aged children. Methods This was a secondary analysis of baseline data collected from a randomized-controlled clinical trial. (ClinicalTrials.gov Identifier: NCT03521349). 7–12-year-old (n = 81) children were recruited from East-Central Illinois. Dual-energy x-ray absorptiometry (DXA) was used to assess visceral adipose tissue (VAT) and whole-body adiposity (%Fat). Weight was obtained to calculated body mass index percentile (BMI %ile). Skin carotenoids were assessed via reflection spectroscopy. Macular carotenoids were assessed as macular pigment optical density (MPOD). Dietary, birth, and breastfeeding information was self-reported by parents. Results Skin carotenoids were inversely related to %Fat (P &lt; 0.01), VAT (P &lt; 0.01) and BMI %ile (P &lt; 0.01). VAT and BMI %ile significantly mediated this relationship between exclusive breastfeeding duration and skin carotenoids, following adjustment for dietary carotenoids, energy intake, and mother education. Conclusions Weight status and adipose tissue distribution mediate the positive correlation between exclusive breastfeeding duration and skin carotenoids among children aged 7–12 years. The results indicate the need to support breastfeeding and healthy physical growth in childhood for optimal carotenoid status.

scholarly journals The impact of bZIP Atf1ortholog global regulators in fungi

2021 ◽  
Author(s):  
Éva Leiter ◽  
Tamás Emri ◽  
Klaudia Pákozdi ◽  
László Hornok ◽  
István Pócsi
Keyword(s):  
Transcription Factors ◽  
Stress Response ◽  
Secondary Metabolite ◽  
Plant Pathogens ◽  
Leucine Zipper ◽  
Secondary Metabolite Production ◽  
Special Focus ◽  
Human Pathogens ◽  
Metabolite Production ◽  
The Impact

Abstract Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. Key points • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.

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