Experimental Physiology最新文献

The aim of the study was to investigate the spinal mechanisms involved in regulating postural balance in humans. Participants stood in a normal stance, with their spinal postural networks either non-invasively activated or not stimulated by electrical stimulation. Postural sway, muscle activity, joint kinematics and respiratory movements were monitored. Half of the participants depended on external sensory cues for controlling balance (field dependent), whereas the other half did not (field independent). Stimulation was performed at the T11-T12 or L1-L2 vertebral level using intensities below the motor threshold. When participants stood without stimulation, differences in body segment movement in the frontal plane were observed between subgroups, in addition to similarities in segment movement in the sagittal plane. Field-dependent participants demonstrated greater mediolateral sway and pelvic motion and relied more on hip involvement in frontal centre of pressure dynamics than field-independent participants. Stimulation at T11-T12 induced changes in muscle activity and body segment coordination in both groups. It led to a reduction in mediolateral sway and enhanced postural stability, but only in field-dependent individuals. Stimulation at L1-L2 altered muscle activity and joint kinematics in both subgroups without having an effect on postural stability. Stimulation did not affect respiratory movements or posture-respiratory coupling. In the human spinal cord, the interneuronal networks involved in postural regulation are located at the T11-T12 level and operate under supraspinal control. Interneuronal networks at the L1-L2 level also modulate muscle activity and body segment coordination; however, their specific role in regulating upright posture remains unclear.

The dynamics of physiological systems are impacted by both exercise and hypoxia. Network models can be used to map the interactions between various physiological components in environmental physiology and exercise using the concepts of information theory. This cross-over study compared three normobaric conditions: control, simulated altitude of 2500 m (fraction of inspired oxygen: $F_{i{O}_2}$ ≈ 15.1%) and 3500 m ( $F_{i{O}_2}$ ≈ 13.5%), and rest vs. isometric exercise through the lens of network physiology. The 12 participants (6 M and 6 F; 22.25 ± 2.42 years; 23.01 ± 3.24 kg/m²) spent ∼30 min in a tent coupled to an altitude simulator, whose last 3 min consisted of a series of nine unilateral isometric maximal contractions of quadriceps. A metabolic system in breath-by-breath mode was used to register cardiorespiratory variables. In-degree, out-degree, and transfer entropy (TE) were computed to capture the information flow between variables. A weighted Jaccard Similarity Index was used to assess network similarities. The increase of ${\dot{V}}_{O_2}$ in exercise over rest was slightly more prominent during hypoxia (P = 0.054, η² _p = 0.232). Normoxia-hypoxia networks were more similar during resting than exercise. Rest-exercise networks were less similar to each other during simulated altitude of ∼2500 m (P = 0.008, η² _p = 0.353). Neither TE during rest nor during exercise nor the $S_{p{O}_2}$ / $F_{i{O}_2}$ ratio significantly predicted the occurrence of symptoms. Unexpectedly, compared to mild-grade hypoxia, low-grade hypoxia induced more changes in physiological connectivity, with the majority of the connections converging on putative hidden nodes that we suggest are oxygen delivery-dependent. Network approaches could offer new developments in exercise and environmental physiology.

There is a category of large-scale neuromusculoskeletal injuries that result in long-term functional disabilities, and one such injury is volumetric muscle loss (VML) injury. In addition to the clinical outcomes related to long-term dysfunction, co-morbidities and reduced mobility and physical activity, this review addresses several underexplored physiological limitations of VML at both the whole-body level and within the injured muscle. Our objectives with this review are to provide: (1) critical understanding of the pathophysiological limitations related to VML injury; (2) evidence for emerging treatment options that target the VML-induced metabolic dysregulation; and (3) early functional data on metabolic treatments as a component of regenerative rehabilitation. We highlight new attempts to intervene in this unique pathophysiology, in addition to current unanswered questions for the field.

Recanalization by endovascular treatment (EVT) is effective in acute ischaemic stroke caused by large-vessel occlusion. Better understanding of the pathophysiology could possibly identify targets for improving peri-procedural management and thereby patient outcome. Dynamic cerebral autoregulation (dCA), which maintains cerebral blood flow despite changes in arterial blood pressure (ABP), is reportedly impaired after EVT. Blood pressure thresholds after EVT have previously been individualized by accounting for dCA, which could improve outcome. The conventional method to estimate dCA requires transcranial Doppler, which is difficult to use during EVT. Instead, we investigated dCA during EVT by near-infrared spectroscopy (NIRS) which is more feasible. NIRS and ABP were measured continuously before recanalization, immediately after recanalization, and after general anaesthesia termination for subsequent transfer function analysis yielding the dCA measure of phase shift (0.07-0.2 Hz). Phase shift did not differ between the ischaemic and contralateral hemisphere but the sensitivity to end-tidal CO₂ was increased in the ischaemic hemisphere immediately after recanalization. Phase shift over time interacted with 90-day functional outcome including independence and mortality. Hence, patients with good long-term outcome showed increased phase shift during and after EVT, while phase shift decreased in poor outcome patients. In conclusion, dCA did not differ between hemispheres during EVT but was more sensitive to end-tidal CO₂ in the ischaemic compared to the contralateral hemisphere and dCA evolved differently in patients with good and poor outcome. Our findings of individual dCA differences during EVT suggest benefit of individualized blood pressure management, which should be addressed in future studies.

Skeletal muscle plays an important role in whole-body health, quality of life and regulation of metabolism. The maintenance of a healthy mitochondrial pool is imperative for the preservation of skeletal muscle quality and is mediated through mitochondrial quality control consisting of mitochondrial turnover mediated by a balance between organelle synthesis and degradation. The selective tagging and removal of dysfunctional mitochondria is essential for maintaining mitochondrial quality control and is termed mitophagy. The mechanisms of the initial stages of mitophagy involving the recognition and tagging of mitochondria within skeletal muscle are well established, but our understanding of the terminal step involving organelle degradation mediated via lysosomes is in its infancy. An assessment of the proteolytic functions to facilitate the removal and breakdown of dysfunctional mitochondria is crucial for our understanding of the mechanisms of mitophagy, which is essential for maintaining skeletal muscle health. The aim of this review is to address the current knowledge surrounding mitophagy and lysosomal function, alongside distinct physiological conditions, such as ageing, exercise and disuse, that have varying effects on mitophagy and lysosomal adaptations within skeletal muscle.

Physical activity is widely recognized for its ability to promote brain health, with acute exercise transiently enhancing cognition and long-term training attenuating cognitive decline. However, the mechanisms underlying these benefits remain incompletely understood. Cerebral blood flow (CBF) has traditionally been considered central to exercise-induced cognitive improvements, given the brain's dependence on a continuous supply of oxygen and glucose. Yet, accumulating evidence indicates that changes in global CBF alone cannot fully explain enhanced cognitive performance. Instead, regional CBF responses through neurovascular coupling, as well as cerebral metabolism - including oxygen extraction, glucose utilization and lactate uptake - are likely more critical determinants of brain function in response to exercise. Importantly, substantial individual differences exist in these responses. While some individuals experience robust cognitive gains from identical exercise regimens, others show little or no benefit. Emerging evidence suggests that variability in glucose tolerance, lactate dynamics and exercise capacity may underlie this heterogeneity, reflecting differences in metabolic responses and cerebrovascular regulation. For example, impaired glucose utilization might be linked to diminished exercise-induced cognitive improvement, whereas lactate uptake appears to support high-intensity exercise-related gains. These findings highlight that the cognitive effects of exercise are not uniform, but rather influenced by individual physiological characteristics. This review therefore emphasizes the integrative regulation of CBF and metabolism as key factors mediating exercise-induced cognitive improvements, while emphasizing the importance of inter-individual variability. Understanding why some individuals benefit more than others is essential for adapting exercise prescriptions to maximize brain health across diverse populations.

Ageing is a risk factor for cardiovascular and neurodegenerative diseases. The myogenic response in resistance arteries is responsible for basal (myogenic) tone and blood flow autoregulation. G-protein-coupled receptors and G₁₂/RhoA/Rho kinase are implicated in myogenic tone (MT), and we aimed to clarify their role in pressure sensing and ageing. We studied MT in third-order mesenteric arteries (MA) ex vivo and first-fourth order cerebral arteries (CA) in vivo in young versus middle-aged male mice. Inhibition of α₁-, AT₁-, ET_A- and TP-receptors and thromboxane synthase did not affect MT in MA from young mice. The P2Y-receptor blocker suramin inhibited MT, whereas PPADS and apyrase did not. MT in intact or endothelium-denuded MAs was not affected by the knockout of P2Y₆-receptor (P2Y₆-R). qPCR showed upregulation of P2Y₂-R in P2Y₆-deficient arteries. MT was not affected in P2Y₂-R knock-out mice. The sphingosine-kinase (SK) blocker SKI-II inhibited MT in young mice, and the sphingosine 1-phosphate receptor 2 (S1P₂-R) blocker JTE-013 inhibited MT in young and middle-aged mice. MT was impaired in middle-aged mice. Furthermore, MT was reduced in young mice carrying familial Alzheimer's disease mutations (5xFAD), and JTE-013 abolished MT in 5xFAD mice and their wild-type littermates. JTE-013 did not affect calcium signalling in cultured human coronary artery smooth muscle cells. High-resolution microangiography confirmed that infusion of JTE-013 or KD025 (a Rho-kinase 2 inhibitor) preferentially dilated small (distal) CAs, and infusion of nifedipine (an L-type channel inhibitor) dilated all CAs in all mice, independent of age. SK and S1P₂-R are crucially involved in pressure sensing in MT. RhoA/Rho-kinase signalling might be involved in age-related MT deficiency.

The leading cause of epilepsy-related mortality is sudden unexpected death in epilepsy (SUDEP), resulting from seizure-induced cardiorespiratory arrest by mechanisms that remain unresolved. Mutations in ion channel genes expressed in both brain and heart represent SUDEP risk factors because they can disrupt neural and cardiac rhythms, providing a unified explanation for seizures and lethal arrhythmias. However, the relative contributions of brain-driven mechanisms, heart-intrinsic processes and seizures to cardiac dysfunction in epilepsy remain unclear. Here, we investigated the heart-specific role of the Kcna1 gene, which encodes Kv1.1 voltage-gated potassium channel α-subunits expressed in both neurons and cardiomyocytes, where they shape action potential firing and influence seizure and arrhythmia susceptibility. We generated cardiac-specific Kcna1 conditional knockout (cKO) mice lacking Kv1.1 selectively in cardiomyocytes and assessed their cardiac function using in vitro and in vivo electrophysiology. Cardiac Kv1.1 deficiency prolonged action potentials in atrial, but not ventricular, cardiomyocytes, demonstrating a direct role for Kv1.1 in atrial repolarization. Despite these cellular effects, cKO mice exhibited normal lifespans, electrocardiographic features, heart rate variability, pacing-induced arrhythmia susceptibility, contractility, seizure susceptibility and seizure-induced mortality. Thus, while loss of cardiac Kv1.1 was sufficient to impair atrial repolarization, it did not reproduce the broader cardiac abnormalities seen in global Kcna1 knockouts. Given the higher mortality rates of global compared with neural-specific knockouts in our previous studies, cardiac Kv1.1 deficiency, while not lethal alone, may increase vulnerability to seizure-related death when combined with neural deficiency, consistent with a brain-heart dyssynergy that lowers the threshold for fatal events.