Journal of applied physiology最新文献

Breathing hyperoxic gas is common in diving and accelerates fatigue after prolonged and repeated exposure. The mechanism(s) remain unknown but may be related to increased oxidants that interfere with skeletal muscle calcium trafficking or impaired aerobic ATP production. To determine these possibilities, C57BL/6J mice were exposed to hyperbaric oxygen (HBO₂) for 4 h on three consecutive days or remained in room air. Postfinal exposure, fatigue was determined by grip strength and run-to-exhaustion tests. Other measurements included indices of oxidant stress and antioxidant defenses, mitochondrial bioenergetics, caffeine-induced sarcoplasmic reticulum-calcium release, and S-nitrosylation of ryanodine receptor 1 (RyR1). Despite grip strength being unaffected by repeated HBO₂ exposure, mean running time was reduced by 50%. In skeletal muscle from HBO₂ exposed mice, superoxide production was significantly increased, resulting in elevated lipid and DNA (nuclear and mitochondrial) oxidation. Accompanying increased oxidant stress was a reduction in glutathione content and increased Sod1 and Hmox1 gene expression; Ucp3 mRNA was reduced. Mitochondrial respiration, mitochondrial membrane potential, and NAD⁺/NADH were not influenced by HBO₂. In contrast, caffeine-induced sarcoplasmic reticulum (SR)-calcium release was reduced by 66% and S-nitrosylation of RyR1 was increased by 45%. Exposing mice to repeated HBO₂ increases oxidant stress that activates some antioxidant defenses. Mitochondrial function is not altered and could be related to decreased production of UCP3 that serves to maintain the electrochemical proton gradient. S-nitrosylation of RyR1 may promote SR-calcium leak and reduce content, a potential mechanism for repeated HBO₂-induced fatigue.NEW & NOTEWORTHY Breathing hyperoxic gas during prolonged and repeated dives causes fatigue but the mechanisms are unknown. Here, we show in mice exposed to repeated hyperbaric oxygen that running fatigue is accelerated and accompanied by increased skeletal muscle oxidant stress and reduced caffeine-induced sarcoplasmic reticulum (SR)-calcium release. The latter may be due to increased S-nitrosylation of ryanodine receptor 1 (RyR1) and be a mechanism for impaired physical performance after repeated oxygen diving.

Serotonin (5-HT) is integral to signaling in areas of the brainstem controlling ventilation and is involved in central chemoreception. Selective serotonin reuptake inhibitors (SSRIs), used to effectively increase 5-HT concentrations, are commonly prescribed for depression. The effects of SSRIs on the control of breathing and the potential influence of cerebral blood flow (CBF) have not been directly assessed. We hypothesized that a single SSRI dose in healthy adults would not impact resting ventilation, global CBF, or brainstem blood flow reactivity to CO₂ but would steepen the slope of the hypercapnic ventilatory response (HCVR). In 15 young, healthy adults (6 females, 25 [Formula: see text] 5 yr, 70 [Formula: see text] 10 kg, 172 [Formula: see text] 15 cm, 24 [Formula: see text] 4 kg/cm²), using a placebo-controlled, double-blind, randomized design, we assessed baseline cardiorespiratory and CBF (duplex ultrasound) responses to SSRI (40 mg citalopram), as well as to hyperoxic hypercapnic rebreathing (as an index of central chemoreception). Baseline measures of mean arterial pressure, heart rate, minute ventilation, CBF, and the pressures of end-tidal oxygen and carbon dioxide were all not influenced by SSRI. Likewise, the sum of blood flowing through both vertebral arteries (as an index of brainstem blood flow) during hypercapnia was also unchanged. In contrast, basal ventilation (during rebreathing following hyperventilation and during hyperoxia) was elevated from 9.5 [Formula: see text] 4.1 to 11.5 [Formula: see text] 5.5 L/min (interaction P = 0.023); and counter to our hypothesis, the central chemoreceptor-mediated ventilatory response to CO₂ was reduced following SSRI from 7.5 [Formula: see text] 5.3 to 5.1 [Formula: see text] 4.1 L/min/mmHg (interaction P = 0.027). The implications of these findings in health and pathology remain to be determined.NEW & NOTEWORTHY Acute inhibition of serotonin reuptake with citalopram diminishes the ventilatory response to hyperoxic hypercapnic rebreathing, possibly indicating decreased sensitivity of the central chemoreceptors and respiratory control centers. Additionally, ventilation during minimal chemoreceptor activation-i.e., following hypocapnia during hyperoxia-is elevated, perhaps signifying an increased tonic activity of the respiratory control areas. These changes appear to be independent of brainstem blood flow. These findings may have implications for antidepressant drug use.

We sought to examine how resistance training (RT) status in young healthy individuals, either well resistance trained (T, n = 10) or untrained (UT, n = 11), affected molecular markers with leg immobilization followed by recovery RT. All participants underwent 2 wk of left leg immobilization via a locking leg brace. Afterward, all participants underwent 8 wk (3 days/wk) of knee extensor-focused progressive RT. Vastus lateralis (VL) ultrasound-derived thickness and muscle cross-sectional area were measured at baseline (PRE), immediately after disuse (MID), and after RT (POST) with VL muscle biopsies also being collected at these time points. Both groups presented lower ultrasound-derived VL size metrics at MID versus PRE (P ≤ 0.001), and values increased in both groups from MID to POST (P < 0.05); however, VL size increased from PRE to POST in UT only (P < 0.001). Mean and type II myofiber cross-sectional area values were greater at PRE and POST versus MID (P < 0.05), with T being greater than UT throughout (P ≤ 0.012). In both groups, satellite cell number was not affected by leg immobilization but increased in response to RT (P ≤ 0.014), with T being greater than UT throughout (P = 0.004). Total RNA (ribosome content) decreased (P = 0.010) from PRE to MID while total RNA and certain endoplasmic reticulum stress proteins increased from MID to POST regardless of training status. Immobilization-induced muscle atrophy and recovery RT hypertrophy outcomes are similar between UT and T participants, and the lack of molecular signature differences between groups supports these findings. However, results are limited to younger adults undergoing noncomplicated disuse.NEW & NOTEWORTHY Formerly trained and untrained individuals demonstrate similar atrophic responses to disuse while untrained individuals exhibited a greater hypertrophic response to subsequent resistance training. The molecular responses accompanying these changes were largely similar between groups and included increases in satellite cell content with resistance training and increases in ribosome biogenesis, which was largely driven by the formerly trained group.

Objective: This study aimed to determine whether interrupting prolonged sitting with brief bouts of light-intensity activity (ISIT), undertaking structured high-intensity interval training (HIIT), or the combination of both interventions would elicit greater cardiometabolic benefits.

Methods: Seventeen healthy adults (22-50 years) were recruited to undertake three 2-week interventions in a random order: i) HIIT (6 HIIT sessions + <5000 steps following the session and on the next day), ii) ISIT (2.5 min light-intensity walking every hour for 12 h/day on weekdays), and iii) HIIT+ISIT. Participants underwent a 6-day lead-in phase prior to each condition (day 1-3: normal activity, day 4-6 sedentary: <5000 steps/day). Pre and post assessments included glycemic control (primary outcome 2-h postprandial glucose), endothelial function via flow-mediated dilation (FMD), cardiorespiratory fitness and body composition. Changes in primary and secondary outcomes were assessed via repeated measures ANOVA.

Results: Eleven participants completed all conditions (8 Female, 33±5 years, 23±4 kg/m², habitual activity 7,156±2,272 steps/day). FMD significantly improved following HIIT+ISIT when compared to ISIT (+1.04±1.20%, p=0.02), but there were no differences when ISIT was directly compared to HIIT. Cardiorespiratory fitness improved significantly following HIIT+ISIT when compared to ISIT (+1.88±2.03 mL/kg/min, p=0.01) but there were no differences when ISIT alone was compared to HIIT. There were no significant differences between groups for outcomes related to glucose control or body composition.

Conclusion: HIIT+ISIT elicits greater improvements in cardiovascular outcomes when compared to ISIT but not HIIT. The benefits of structured exercise, such as HIIT, may go beyond those achieved by limiting sedentary behavior alone.

Exercise in heart failure with preserved ejection fraction (HFpEF) remains a hot topic, although current treatment strategies have not been shown to improve the long-term prognosis of HFpEF. Previous studies have mostly focused on the roles of endurance training, the mechanisms underlying long-term voluntary exercise have not been elucidated. The purpose of the present analysis was to evaluate alterations in cardiac function in HFpEF mice (HFpEF-Sed) after 6 weeks of voluntary running (HFpEF-Ex), investigate mechanisms, and compare the effects with fluoxetine (HFpEF-FLX). We found that voluntary exercise, instead of fluoxetine intervention, significantly improved left ventricular end-diastolic internal diameter (LVIDd) and the rate of change in anterior wall thickness (ATW) in HFpEF mice. The exercise capacity of HFpEF-Sed mice was significantly reduced, but prolonged voluntary running significantly reversed the expression of myocardial BNP, TNF-α, and IL-6, α-MHC, and β-MHC in HFpEF-Sed mice, along with myocardial fiber disorders accompanied by massive inflammatory cell infiltrates. Importantly, myocardial Complex III and Complex V, Mfn2, Drp1, p62, and LC3 II/I expression in HFpEF-Sed mice were all significantly different from those of normal mice, whereas voluntary exercise significantly reversed these expressions. These findings strongly suggest that long-term voluntary exercise is effective in avoiding acute and chronic energy stress in HFpEF-Sed mice, which is consistent with the mechanism of current first-line treatment for HFpEF. This notion was further supported by electron microscopy results, which showed no pathological features in cardiomyocyte mitochondrial morphology after prolonged voluntary exercise. Additionally, fluoxetine was found to inhibit depressive-like behavior in HFpEF mice.

Impaired glycemic control increases the risk for type 2 diabetes (T2D) and Alzheimer's Disease (AD). Heat therapy (HT), via hot water immersion (HWI), has shown promise in improving shared mechanisms implicated in both T2D and AD, like blood glucose regulation, insulin sensitivity, and inflammation. The potential for HT to improve brain health in individuals at risk for AD has not been examined. This pilot study aimed to assess the feasibility and adherence of utilizing HT in cognitively healthy older individuals at risk for AD due to existing metabolic risk factors. Participants underwent four weeks of HT (three sessions/week) via HWI, alongside cognitive screening, self-reported sleep characterization, glucose tolerance tests, and MRI scans pre- and post-intervention. A total of 18 participants (9 male, 9 female; mean age: 71.1 ± 3.9 years), demonstrating metabolic risk, completed the intervention. Participant adherence for the study was 96% (8 missed sessions out of 216 total sessions), with one study related mild adverse event (mild dizziness/nausea). Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. Secondary outcomes of the HT intervention demonstrated significant changes in mean arterial pressure, diastolic blood pressure, and cerebral blood flow p<0.05), with a trend toward improved body mass index (p=0.06). Future studies, including longer durations and a thermoneutral control group, are needed to fully understand heat therapy's impact on glucose homeostasis and potential to improve brain health.

Objective: We investigated the associations of ongoing, chronic stress exposure and stress appraisal on vascular endothelial function (VEF) in young adults. Methods: In 72 healthy young adults (74% female; age = 25±1 y), we assessed chronic stress exposure and appraisal with a measure that quantified chronic stress exposure and chronic stress appraisal related to 8 specific stressors over the last year. Participants completed the perceived stress scale (PSS) as a measure of global, proximal stress appraisal. VEF was assessed using the brachial artery flow mediated dilation technique. We examined relations among ongoing, chronic stress exposure and stress appraisal versus VEF adjusted for age and sex, and then assessed whether stress appraisal moderated the effect of chronic stress exposure on VEF. Results: Chronic stress exposure (β=-0.24, p=.045), but not chronic stress appraisal (β=0.07, p=.56) or perceived stress (β=-0.20, p=.11), was related to VEF. Perceived stress (p = .046), but not chronic stress appraisal (p=.54), moderated the association between chronic stress exposure and VEF. The effect of chronic stress exposure on VEF ceased to be significant at a PSS score of ~22. Subsequent exploratory stratified analysis indicated that those with PSS ≥22 had increased exposure to adverse childhood experiences (+1.6±0.6, p=.01), greater depressive symptoms (+10.2±2.7, p<.001), and reduced psychological resilience (-7.6±3.5, p=.036). Conclusions: Chronic stress exposure significantly predicts impaired VEF among young adults. Further, this relation is influenced by proximal perceived stress, such that the association of chronic stress exposure on VEF may be obscured at high levels of proximal perceived stress.

The present study assessed whether single-leg daily blood flow restriction (BFR) treatment attenuates the decline in muscle fiber size, capillarization, and satellite cell (SC) content during 2 wk of bed rest in healthy, young men. Twelve healthy, young men (age: 24 ± 3 yr; BMI: 23.7 ± 3.1 kg/m²) were subjected to 2 wk of bed rest, during which one leg was exposed to three times daily 5 min of BFR, whereas the contralateral leg received sham treatment [control (CON)]. Muscle biopsies were obtained from the m. vastus lateralis from both the BFR and CON legs before and immediately after 2 wk of bed rest. Types I and II muscle fiber size, myonuclear content, capillarization, and SC content were assessed by immunohistochemistry. No significant decline in either type I or type II muscle fiber size was observed following bed rest, with no differences between the CON and BFR legs (P > 0.05). Type I muscle fiber capillary density increased in response to bed rest in both legs (P < 0.05), whereas other muscle fiber capillarization measures remained unaltered. SC content decreased in both type I (from 7.4 ± 3.2 to 5.9 ± 2.7 per 100 fibers) and type II (from 7.2 ± 3.4 to 6.5 ± 3.2 per 100 fibers) muscle fibers (main effect of time P = 0.018), with no significant differences between the BFR and CON legs (P > 0.05). In conclusion, 2 wk of bed rest has no effect on muscle capillarization and decreases the SC content, and daily BFR treatment does not affect skeletal muscle fiber size and SC content in healthy, young men.NEW & NOTEWORTHY We recently reported that the application of daily blood flow restriction (BFR) treatment does not preserve muscle mass or strength and does not modulate daily muscle protein synthesis rates during 2 wk of bed rest. Here, we show that 2 wk of bed rest resulted in a decrease in satellite cell (SC) content. In addition, the BFR treatment did not affect muscle fiber size, capillarization, and SC content during 2 wk of bed rest.

Chronic exposure to shortened sleep is associated with an increased risk of Alzheimer's disease and dementia. Previous studies show insufficient (e.g., poor or fragmented) sleep impairs cerebrovascular reactivity to metabolic stress and may have a detrimental effect on the link between cerebral blood flow (CBF) and neural activity (i.e., neurovascular coupling, NVC). The purpose of this study was to examine the effect of acute sleep restriction on CBF in response to a metabolic (carbon dioxide, CO₂) and a cognitive stressor. We hypothesized sleep restriction (4-h time in bed) would attenuate CBF and NVC. Sixteen young adults (8 M/8 F, 28 ± 8 yr, 25 ± 3 kg/m²) completed two morning visits following a night of normal (7.38 ± 0.82 h) or restricted (4.27 ± 0.93 h, P < 0.001) sleep duration. Middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) was measured at rest and during 1) 5 min of carbogen air-breathing and 2) five trials consisting of a period of eyes closed (30 s), followed by eyes open (40 s) while being challenged with a validated visual paradigm (Where's Waldo). Baseline MCAv was unaffected by acute sleep restriction (control: 64 ± 14 cm/s; restricted 61 ± 13 cm/s; P = 0.412). MCAv increased with CO₂; however, there was no effect of restricted sleep (P = 0.488). MCAv increased in response to visual stimulation; the peak NVC response was reduced from control following restricted sleep (control: 16 ± 12%; restricted: 9 ± 7%; P = 0.008). Despite no effect of acute sleep restriction on resting CBF or the response to CO₂ in young men and women, NVC was attenuated following a night of shortened sleep. These data support an important role for sleep in NVC and may have implications for the development of neurodegenerative disease states, such as Alzheimer's and dementia.NEW & NOTEWORTHY Chronic exposure to shortened sleep is associated with an increased risk of Alzheimer's disease and dementia. We examined the effect of acute sleep restriction (4-h time in bed) on cerebral blood flow in response to a metabolic (carbon dioxide) and a cognitive stimulus. Despite no effect of acute sleep restriction on resting cerebral blood flow or the response to carbon dioxide in young men and women, neurovascular coupling was attenuated following a night of shortened sleep.

The aim of this study is to investigate the differential impacts of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on neural circuit dynamics and neuronal firing in the hippocampal CA1 subregion (CA1) region and medial entorhinal cortex (MEC) of mice. Forty-two male ICR mice were randomized into control, HIIT, and MICT groups. Electrophysiological recordings were performed pre- and postintervention to assess neural circuit dynamics and neuronal firing patterns in the CA1-MEC pathway. Both exercise protocols increased local field potential (LFP) coherence, with MICT showing a more pronounced effect on δ and γ coherences (P < 0.05). Both modalities reduced δ power spectral density (PSD) (HIIT, P < 0.05; MICT, P < 0.01) and elevated θ, β, and γ PSDs. Neuronal firing frequency improved in both CA1 and MEC following HIIT and MICT (P < 0.05). HIIT enhanced firing regularity in CA1 (P < 0.05), whereas MICT improved regularity in both regions (P < 0.05). Both protocols reduced firing latency (HIIT, P < 0.05; MICT, P < 0.01) and enhanced burst firing ratio, interburst interval (IBI), burst duration (BD), and LFP phase locking (P < 0.05 or P < 0.01). Notably, MICT significantly improved spatial working memory and novel recognition abilities, as evidenced by increased novel arm time, entries, and preference index (P < 0.01). This study reveals that both HIIT and MICT positively impact neural processing and information integration in the CA1-MEC network of mice. Notably, MICT exhibits a more pronounced impact on neural functional connectivity and cognitive function compared with HIIT. These findings, coupled with the similarities in hippocampal electrophysiological characteristics between rodents and humans, suggest potential exercise-mediated neural plasticity and cognitive benefits in humans.NEW & NOTEWORTHY This study is the first to investigate HIIT and MICT's effects on neural activity in the mouse CA1-MEC circuit, demonstrating that exercise modulates processing, enhances integration, and boosts cognitive performance. Due to similar hippocampal electrophysiology in rodents and humans during movement and navigation, our findings suggest implications for human brain neural changes, advancing the understanding of neurophysiological mechanisms underlying exercise-cognition interactions and informing exercise recommendations for cognitive health.