Experimental Physiology最新文献

It is widely held that in human, fibres of the corpus callosum mediate inter-hemispheric inhibition - deemed necessary to prevent a bilateral cerebrum from generating simultaneous and potentially conflicting outputs. Ostensible support comes from an electrophysiological phenomenon whereby the mean magnitude of 'test' motor evoked potentials (MEPs) obtained in response to magnetic stimuli delivered over the contralateral motor cortex is diminished when initial 'conditioning' magnetic stimuli have been applied 6-15 ms previously to the opposite motor cortex. A contrary view is that this phenomenon masks, rather than reveals, normal physiological processes. An alternative hypothesis is that cortical motor centres giving rise to efferent projections onto motoneurons innervating homologous muscles conduct reciprocal shaping of excitation. This hypothesis was examined in a large sample (205 participants) by correlating the amplitude of MEPs elicited by a conditioning stimulus (CS) with the amplitude of those elicited 10 ms later by a test stimulus (TS). The magnitudes of responses to the CS and TS were positively correlated. This remained the case following statistical compensation for an observed covariation of low amplitude fluctuations in the background (<2 µV root mean squared) electromyographic activity recorded in the (homologous) target muscles prior to stimulation. Although the coefficients representing the magnitude of association between responses to the CS and TS are small (rho < 0.20), they are reliable. These findings support the hypothesis that there is positive covariation in the excitability of corticospinal projections from the two cerebral hemispheres to homologous muscles of the upper limb.

Sustainable development is a growing global concern, but university students in scientific fields such as Physiology struggle to see its direct relevance to their studies. This research explores how an authentic assessment can integrate the United Nations (UN) sustainable development goals (SDGs) into Physiology education. Students were tasked to design and present a group poster on the connections between an SDG and Physiology. Through a mixed-methods approach utilizing questionnaires, pre- and post-assignment data were collected and the students' perceptions of the links and learning opportunities explored. Students reported a shift in how they perceived the intersection between Physiology and societal issues, with many expressing a newfound passion for sustainability. Awareness and understanding of the SDGs increased significantly (19% and 36%, respectively). Students made connections between Physiology and goals such as No Poverty (SDG1), Quality Education (SDG4), Gender Equality (SDG5), and Climate Action (SDG13). Thirteen of the 17 SDGs were rated as significantly more relevant to Physiology after the assignment, among these, several less obviously related goals like Affordable and Clean Energy (SDG7), Sustainable Cities and Communities (SDG11), Responsible Consumption and Production (SDG12), and Partnership for the Goals (SDG17). The remaining four (SDGs 2, 3, 6 and 15) had high initial relevance ratings, which did not significantly change, serving as an internal control supporting the validity of the observed increases for other goals. Responses to open questions suggested that the students' experience of the assessment was rich in context and meaning, making Physiology more than 'just being a uni topic'.

Prolonged exposure to microgravity, simulated via 6° head-down tilt bed rest (HDT), induces musculoskeletal deconditioning and negatively impacts body composition. This study evaluated whether a combination of aerobic exercise with artificial gravity (AG) offers superior protection in comparison to exercise alone. Twenty-four healthy male participants completed 60 days of HDT, randomized into control (C), exercise-only (EX) and exercise with AG (EX-AG) groups. Muscle volume, intramuscular fat, body composition and isokinetic strength were assessed via whole-body MRI and isokinetic dynamometry. All groups experienced thigh fat-free muscle volume loss: C (10.5% ± 2.6%), EX (6.9% ± 2.4%) and EX-AG (4.3% ± 2.4%), with EX-AG showing significantly less atrophy than C (p < 0.001). Compared with C, EX-AG preserved more muscle in both anterior (p  <  0.001) and posterior (p < 0.05) compartments, whilst EX preserved more muscle only anteriorly (p < 0.05). The fat ratio increased more in C (8.9% ± 6.0%) compared with EX-AG (-0.8% ± 3.8%; p < 0.05) but not EX (6.5% ± 9.8%). Muscle fat infiltration increased across all groups (C, 7.0% ± 3.7%; EX, 6.2% ± 4.3%; EX-AG, 3.1% ± 4.7%) but was not different between groups (p > 0.05). Maximal isokinetic torque decreased in all groups over all measured angular velocities but was not different between groups (p > 0.05). This is the first study to investigate the combination of AG and exercise as a countermeasure to body composition changes induced by long-term bed rest. We showed that EX-AG provided partial protection against muscle atrophy and fat accumulation but did not outperform exercise alone in preserving muscle quality, strength or overall body composition.

Transcutaneous spinal cord stimulation, as used for rehabilitation of impaired motor function after spinal cord injury, often involves a 10-kHz waveform modulated to produce repetitive bursts of stimulation. Kilohertz-frequency waveforms may facilitate the summation of subthreshold depolarisations, but the optimal burst duration for nerve stimulation has not been systematically investigated. In 11 adults, the ulnar nerve was stimulated transcutaneously with a 10-kHz waveform that contained 1, 2, 4, 6, 8 or 10 pulses, in random order. Compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) were measured from motor threshold up to the maximal CMAP (M_max). The efficacy of each waveform was determined at M_max as CMAP amplitude divided by total phase charge. For CMAPs and SNAPs, increasing the number of pulses shifted the stimulus-response curves to the left for current and to the right for total charge. Accordingly, an increase in the number of pulses decreased the current but increased the total charge at sensory and motor thresholds and M_max. Efficacy decreased as the number of pulses increased. Onset latencies were delayed for waveforms with six or more pulses compared to a single pulse. These findings provide evidence of the summation of subthreshold depolarisations in sensory and motor axons in humans. However, the optimal number of pulses for summation remains unclear due to the opposing changes in current and total charge. It is clear, though, that more than six pulses is suboptimal, as there were no further decreases in threshold current while total charge continued to increase.

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.

This study aimed to determine whether sodium nitrite supplementation prevented chronic stress-induced cerebrovascular dysfunction and cognitive decline. We hypothesize that nitrite supplementation will prevent the oxidative environment and cerebrovascular dysfunction associated with chronic stress and maintain cognitive health. Eighteen-week-old male/female C57BL/6 mice underwent 8 weeks of control conditions or unpredictable chronic mild stress (UCMS) with or without sodium nitrite (50 mg/L) in the drinking water. Excised middle cerebral arteries (MCA) were mounted in a pressurized myobath and exposed to increasing concentrations of acetylcholine (ACh). Nitrite supplementation prevented the UCMS-induced impaired ACh response in the MCA. We examined xanthine oxidoreductase (XOR) as a potential mechanism by determining XOR protein abundance, activity, and hydrogen peroxide production in the liver and brain. Nitrite supplementation prevented the development of an oxidative environment within the liver, brain and cerebrovasculature. Assessment of working memory revealed that sodium nitrite did not fully prevent the impairment of cognitive function because of chronic stress. These data suggest that nitrite supplementation protects against stressed-induced cerebrovascular dysfunction by limiting the actions of oxidants, potentially via XOR, while improving NO bioavailability. However, nitrite was not sufficient to prevent cognitive impairment with chronic stress.

Poor maternal nutrition and excessive gestational weight gain predict future development of obesity in offspring. Preclinically, maternal obesity induced by a high-fat, high-sugar diet (HFHSD) induces hyperphagia and obesity in offspring. We hypothesized that this might, in part, reflect reduced peripheral gastric vagal afferent (GVA) satiety signalling. Female Glu Venus mice were fed a standard laboratory diet (SLD) or HFHSD for 11 weeks before mating and throughout pregnancy and lactation. Offspring were weaned onto a SLD, then housed in metabolic cages at 6-7 weeks old to assess feeding behaviour. In vitro single-fibre GVA recordings were conducted on tissue collected from 8-week-old mice. Before mating, HFHSD dams were 13% heavier, with 66% higher relative fat mass compared with SLD dams. Maternal diet had no impact on total food intake or offspring weight. Meal size during the light phase was 14% larger in HFHSD than control offspring. Meal duration was longer in HFHSD than control offspring of both sexes across 24 h and the dark phase, and in females during the light phase. HFHSD offspring ate fewer meals than control offspring across all time periods. Tension-sensitive GVAs responded less to stretch in male, but not female, HFHSD than SLD offspring. Mucosal GVA responses to mucosal stroking were unaffected by maternal diet or offspring sex. In conclusion, exposure in utero and during lactation to elevated maternal adiposity and maternal HFHSD consumption induces male-specific programming of reduced GVA responses to stretch. Meal size was increased in both sexes only during the light phase, suggesting programming of other appetite-regulatory pathways by this exposure.

After reaching sexual maturity, uterine function is driven by cyclical variations in hormone levels. The electrical and mechanical activity in the uterus varies during the menstrual cycle, contributing to essential functions such as sperm transport and shedding the menstrual lining. However, there is a lack of quantification of the variation in uterine function occurring over the course of the cycle. Female Wistar rats were used to quantify the changes in uterine electrical activity in vivo with respect to the oestrous cycle. Under anaesthesia, the uterus was exteriorised, and electrodes were placed on the dorsal and ventral sides of the organ to record spontaneous activity from the serosa. Electrical events were separated into slow and fast components based on frequency. The duration and interval between events were measured and propagation directions and velocities were mapped along the uterus using high spatial resolution electrode arrays. All stages of the oestrous cycle showed ovarian-cervical propagation, but cervical-ovarian propagation was also present in pro-oestrus and metoestrus. Ovarian-cervical propagation was dominant in oestrus and metoestrus. The interval between events showed significant differences with 40.2 ± 5.6 s (1.51 ± 0.25 cpm) and 60.5 ± 2.6 s (1.02 ± 0.05 cpm) during the dioestrus and metoestrus phases, respectively (P < 0.001). The slow and fast component durations were similar across the oestrous cycle (19.9 ± 2.2 s and 10.2 ± 3.0 s, respectively). This emphasizes the role of the oestrous cycle in guiding uterine function through modulation of the electrical activity and shows potential for estimating the oestrous cycle phases based on electrical characteristics.

Unpredictable gait disturbances, particularly in the mediolateral direction, pose a significant challenge to stability and are a common contributor to falls. Although the corticospinal tract is critical for gait and postural control, its response to such instabilities remains unclear. To investigate if corticospinal excitability increases during laterally destabilised gait, single-pulse transcranial magnetic stimulations were delivered over the primary motor cortex of 15 healthy individuals during steady-state and laterally destabilised treadmill gait. Full-body kinematics were recorded using an optoelectronic motion capture system. Stimulations with coil displacement >5 mm from the targeted location were excluded. Corticospinal excitability was quantified for four upper- and three lower-leg muscles by the motor evoked potential (MEP) amplitude and compared between steady-state and destabilised gait. Destabilisation resulted in a wider step width and shorter stride duration with increased variability and greater dynamic instability. Foot placement control was increased at mid-swing, along with greater average foot placement error. No differences in corticospinal excitability were observed in the lower-leg muscles. All upper-leg muscles demonstrated greater absolute MEPs in destabilised relative to steady-state gait. After normalising MEP to the pre-stimulus muscle activity, these periods became less pronounced; however, increases were observed in all but the gastrocnemius muscles. These findings suggest heightened readiness of the corticospinal tract projecting to upper-leg muscles during destabilised gait, which could reflect general stabilising strategies such as decreasing stride time and increasing step width.