Experimental Physiology最新文献

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Ageing-related neuromuscular dysfunction is associated with reduced tropomyosin-related kinase receptor subtype B (TrkB) signalling and accumulation of damaged cytoplasmic aggregates in motor neurons. Autophagy functions to remove these damaged aggregates, and we previously reported increased cervical motor neuron expression of LC3 and p62 in old age. We hypothesized that inhibition of TrkB kinase activity results in an increase in the relative expression of both LC3 and p62 in cervical motor neurons, consistent with impaired progression of autophagy. TrkB^F616A mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were treated at 6, 18 or 24 months of age with vehicle or 1NMPP1 for 7 days. Immunofluorescence intensity was measured to determine LC3 and p62 expression in choline acetyltransferase-positive motor neurons in the cervical spinal cord. The effect of inhibiting TrkB kinase activity on progression of autophagy was age dependent. In 6-month-old mice, inhibiting TrkB kinase activity increased cervical motor neuron expression of LC3 by 11% (P < 0.001) and p62 by 8% (P = 0.019) compared with vehicle treatment. In 18- and 24-month-old mice, there was no effect of inhibiting TrkB kinase activity on motor neuron LC3 or p62 expression. We provide evidence that inhibition of TrkB signalling impairs progression of autophagy in motor neurons of young mice, similar to the response to ageing. Accordingly, a reduction of TrkB signalling in old age might contribute to neuromuscular dysfunction by impairing progression of autophagy in motor neurons.

Position sense is arguably more important than any of the other proprioceptive senses, because it provides us with information about the position of our body and limbs in relationship to one another and to our surroundings; it has been considered to contribute to our self-awareness. There is currently no consensus over the best method of measuring position sense. We have recently measured position sense with three commonly used methods. These were two-arm matching, one-arm pointing and one-arm repositioning, all carried out by blindfolded subjects with their lightly loaded forearms moving in the sagittal plane. It is currently believed that muscle spindles are the principal position sensors. We posed the question, was there evidence for spindles participating in the generation of position sense with each method? The indicator of spindle activity we used was the presence of thixotropic errors in the position signal, in response to conditioning voluntary contractions of forearm muscles. Based on this criterion, there was evidence of spindles contributing to position sense with all three methods. It was concluded that the spindle contribution to the position signal and the extent to which this was processed centrally was different with each method. It is argued that a case could be made for the existence of more than one position sense. Differences between the methods have implications for their meaning in a clinical setting.

Less than 7% of the world's population live at an altitude above 1500 m. Yet, as many as 67% of medalists in the 2020 men's and women's Olympic marathon, and 100% of medalists in the 2020 men's and women's Olympic 5000 m track race may have been born or raised above this otherwise rare threshold. As a possible explanation, research spanning nearly a quarter of a century demonstrates that indigenous highlanders exhibit pulmonary adaptations distinct from their lowland counterparts. These adaptations may then promote endurance performance. Indeed, healthy indigenous highlanders often exhibit a larger aerobic exercise capacity compared to sea-level residents who travel to high altitude. However, questions remain on whether high-altitude birth is advantageous for sea-level competitions. In this review, we ask whether being born at a high altitude generates an ergogenic advantage for endurance performance in the Summer Olympics-a venue that is generally held at sea level. In so doing, we distinguish between three groups of high-altitude residents: (i) the indigenous highlander, (ii) the highland newcomer, and (iii) the highland sojourner. Concentrating specifically on altitude-induced alterations to pulmonary physiology beginning in the perinatal period, we propose that if altitude-related maladaptations are avoided, genomic and developmental alterations accompanying highland birth may present benefits for endurance competitions at sea level.

We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (n = 10) and wild-type (n = 8) mice, as models of intrinsically 'low' and 'normal' AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromatography with tandem mass spectrometry, with the Search Tool for the Retrieval of Interacting Genes/Proteins database used to generate protein-protein interaction (PPI) networks and enrichment analyses. AC was significantly associated (P-values ranging from 0.0002 to 0.049) with 73 (McArdle) and 61 (wild-type) proteins (r-values from -0.90 to 0.94). These proteins were connected in PPI networks that enriched biological processes involved in skeletal muscle structure/function in both groups (false discovery rate <0.05). In McArdle mice, the proteins associated with AC were involved in skeletal muscle fibre differentiation/development, lipid oxidation, mitochondrial function and calcium homeostasis, whereas in wild-type animals AC-associated proteins were related to cytoskeleton structure (intermediate filaments), cell cycle regulation and endocytic trafficking. Two proteins (WEE2, THYG) were associated with AC (negatively and positively, respectively) in both groups. Only 14 of the 132 proteins (∼11%) associated with AC in McArdle or wild-type mice were also associated with those previously reported to be modified by aerobic training in these mice, providing preliminary evidence for a large divergence in the muscle proteome signature linked to aerobic training or AC, irrespective of AC (intrinsically low or normal) levels. Our findings might help to gain insight into the molecular mechanisms underlying AC at the muscle tissue level.

A maximal apnoea provides significant challenges to one's physiological systems, including significantly altered arterial blood gases, and requires a highly integrative response from multiple systems, that is, changes in blood pressure, maintenance of cerebral blood flow, etc. Previous work and reviews have focused on the cardiovascular responses to a maximal apnoea, but very little work has focused upon the responses of the respiratory muscles and respiratory mechanics. This is important because of the changes to arterial blood gases leading to an increased drive to breath and the appearance of involuntary respiratory muscle contractions. This review outlines what is known about how the respiratory system responds to a maximal apnoea. We put forth the hypothesis that the respiratory muscles may become fatigued following a maximal apnoea and that the respiratory muscles of elite divers may be more fatigue-resistant, which could be an important feature of these individuals which allows them to be successful in this sport. Finally, we provide direction for future work to explore the long-term health of apnoea diving.

The present review aimed to investigate the effectiveness of aerobic exercise (AE) compared to other interventions in decreasing pain intensity and reducing disability in individuals with neck pain. A systematic review (SR) of randomized controlled trials was conducted. This SR was registered in PROSPERO (CRD42021231231). Searches were conducted in five electronic databases (MEDLINE, Embase, CINAHL, Cochrane and SCOPUS). Studies were selected if they included adults over 18 years old with neck pain. The primary outcomes were pain intensity and physical function. A meta-analysis was conducted when applicable. Cochrane RoB Tool-2 was used to determine the risk of bias of included studies, and the certainty of the evidence was determined using the GRADE approach. Out of 4669 initial records screened, six studies published in 12 articles were included. AE was not statistically different compared to no-treatment or other interventions (e.g., localized exercise or acupuncture) on pain intensity measured with a visual analogue scale (VAS) (mean difference (MD) [95%CI]: 5.16 mm [-6.38, 16.70]). Contrarily, strengthening exercise was better than AE for pain intensity (MD [95%CI]: -11.34 mm [-21.6, -1.09]) after treatment. However, when AE was combined with other therapy (strengthening exercises or acupuncture), the combined therapy was better than isolated treatments (MD [95%CI]: 7.71 mm [1.07, 14.35]). A high heterogeneity was observed between protocols, comparisons, and results (magnitudes and directions). In conclusion, AE had positive results only when combined with other therapies to reduce pain intensity and disability in patients with neck pain. However, the evidence is limited, low-quality, and heterogeneous.

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk. During menopause, reductions in nitric oxide (NO) bioavailability, endothelial dysfunction, increases in systemic inflammation, oxidative stress, and impaired vascular remodelling may contribute towards an accelerated decline in the function of cerebral and peripheral vascular systems. Historically, hormone therapy (HT) has been used as a means of managing vascular disease risk and reducing menopause-associated vasomotor symptoms such as hot flushes, though some studies suggest regular exercise has the potential to be a promising alternative. Regular aerobic exercise during early postmenopause may slow vascular decline by improving NO and oestradiol bioavailability, promoting positive vascular remodelling and lowering systemic inflammation. However, exercise-mediated improvements in markers of vascular function are not consistently observed in oestradiol-deficient postmenopausal women. Emerging evidence suggests that due to the greater oestradiol bioavailability during early postmenopause, vascular adaptations to exercise may be enhanced during this stage, as opposed to late postmenopause. Subsequently it may be important to begin regular exercise in the years preceding and immediately following the final menstrual period to slow the progression of vascular disease risk during perimenopause and beyond. The present review will provide a summary of our current understanding of how vascular function is affected during menopause and the role of regular aerobic and resistance exercise training in managing vascular disease risk.

This study applied alterations in partial pressure of end-tidal carbon dioxide ( $P_{\mathrm{ETC}{O}_2}$ ) to challenge dynamic cerebral autoregulation (dCA) responses across the cardiac cycle in both biological sexes. A total of 20 participants (10 females and 10 males; aged 19-34 years) performed 4-min bouts of repeated squat-stand manoeuvres (SSMs) at 0.05 and 0.10 Hz (randomized orders) with $P_{\mathrm{ETC}{O}_2}$ clamped at ∼40 mmHg. The protocol was repeated for hypercapnic (∼55 mmHg) and hypocapnic (∼20 mmHg) conditions. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) were insonated via transcranial Doppler ultrasound. Dynamic end-tidal forcing clamped $P_{\mathrm{ETC}{O}_2}$ , and finger photoplethysmography quantified beat-to-beat changes in blood pressure. Linear regressions were performed for transfer function analysis metrics including power spectrum densities, coherence, phase, gain and normalized gain (nGain) with adjustment for sex. During hypercapnic conditions, phase metrics were reduced from eucapnic levels (all P < 0.009), while phase increased during the hypocapnic stage during both 0.05 and 0.10 Hz SSMs (all P < 0.037). Sex differences were present with females displaying greater gain and nGain systole metrics during 0.10 Hz SSMs (all P < 0.041). Across $P_{\mathrm{ETC}{O}_2}$ stages, females displayed reduced buffering against systolic aspects of the cardiac cycle and augmented gain. Sex-related variances in dCA could explain sex differences in the occurrence of clinical conditions such as orthostatic intolerance and stroke, though the effect of fluctuating sex hormones and contraceptive use on dCA metrics is not yet understood.