Experimental Physiology最新文献_第2页

Optogenetic methods to stimulate gamma motor neuron axons ex vivo.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-02-03 DOI: 10.1113/EP092359

Apoorva Karekal, Remie Mandawe, Cameron Chun, Sai Kiran Byri, Danitza Cheline, Serena Ortiz, Shawn Hochman, Katherine A Wilkinson

{"title":"Optogenetic methods to stimulate gamma motor neuron axons ex vivo.","authors":"Apoorva Karekal, Remie Mandawe, Cameron Chun, Sai Kiran Byri, Danitza Cheline, Serena Ortiz, Shawn Hochman, Katherine A Wilkinson","doi":"10.1113/EP092359","DOIUrl":"https://doi.org/10.1113/EP092359","url":null,"abstract":"It is challenging to stimulate gamma motor neurons, which are important regulators of muscle spindle afferent function, without also recruiting alpha motor neurons. Here, we test the feasibility of stimulating gamma motor neuron axons using optogenetics in two transgenic mouse lines. We used an ex vivo muscle-nerve preparation in adult mice to monitor muscle spindle afferent firing, which should increase in response to gamma motor neuron-induced lengthening of the sensory region of the muscle spindle. A force transducer measured alpha motor neuron-mediated twitch contractions. Blue LED light (470 nm; 1-5 mW) was delivered via a light guide to the sciatic nerve. We confirmed that the more slowly conducting gamma motor neurons were recruited first in mice expressing channelrhodopsin 2 in choline acetyltransferase-positive motor neurons, whereas alpha motor neurons required higher optical intensities, enabling co-activation of alpha and gamma motor neurons depending on light intensity. However, this approach cannot isolate gamma motor neuron activity completely. Cre-dependent channelrhodopsin 2 optoactivation using the putative gamma motor neuron marker neuronal PAS domain protein 1 (Npas1) also increased muscle spindle afferent firing rates and caused only small twitch contractions. This provides functional validation that Npas1 is present primarily in gamma motor neurons and can be used to manipulate gamma motor neurons independently. We propose optogenetic stimulation as a promising tool to manipulate gamma motor neuron activity.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Twin Cycle Hypothesis of type 2 diabetes aetiology: From concept to national NHS programme.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-02-03 DOI: 10.1113/EP092009

Roy Taylor

{"title":"The Twin Cycle Hypothesis of type 2 diabetes aetiology: From concept to national NHS programme.","authors":"Roy Taylor","doi":"10.1113/EP092009","DOIUrl":"https://doi.org/10.1113/EP092009","url":null,"abstract":"The development of magnetic resonance methods for quantifying intra-organ metabolites has permitted advances in the understanding of fasting and post-prandial carbohydrate and lipid handling in people with and without type 2 diabetes. Insulin resistance in the liver was shown to be related to excess intra-organ fat and was able to be returned to normal by weight loss. The practical effect of having muscle insulin sensitivity in the lower part of the wide normal range resulted in the obligatory shunting of carbohydrates via de novo lipogenesis into saturated fat. These observations provided the basis for the Twin Cycle Hypothesis of the aetiology of type 2 diabetes. Subsequent studies on people with type 2 diabetes confirmed the postulated pathophysiological abnormalities and demonstrated their reversibility by dietary weight loss of 10-15 kg. Overall, the fundamental understanding of the mechanisms causing type 2 diabetes has bridged physiological and clinical perspectives. Large population-based randomised controlled trials confirmed the practical clinical application of the method of achieving substantial weight loss, and an NHS programme is now in place offering potential remission to people within 6 years of diagnosis.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vascular health and exercise in females throughout the lifespan: Exploring puberty, pregnancy and menopause.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-30 DOI: 10.1113/EP092170

Kathleen B Miller, M Erin Moir, Brandon G Fico

引用次数: 0

Cardiac muscle contracts more efficiently at lower contraction frequencies.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-29 DOI: 10.1113/EP092367

Toan Pham, Andrew J Taberner, June-Chiew Han

{"title":"Cardiac muscle contracts more efficiently at lower contraction frequencies.","authors":"Toan Pham, Andrew J Taberner, June-Chiew Han","doi":"10.1113/EP092367","DOIUrl":"https://doi.org/10.1113/EP092367","url":null,"abstract":"This study investigated how contraction frequency impacts the mechano-energetics of cardiac muscle performing mechanical work. Left-ventricular trabeculae were isolated from rat hearts and mounted in our work-loop calorimeter to assess their function at physiological temperature (37°C) across three stimulation frequencies, 2 Hz, 3.5 Hz and 5 Hz, in a randomised sequence. Each trabecula was subjected to two experimental protocols: work-loop contractions under a range of afterloads and isometric contractions under a range of muscle lengths. Two contraction protocols allowed the partition of the various components of energy expenditure during cardiac contraction. By simultaneously measuring force-length work and heat output, mechanical efficiency was calculated over a range of afterloads to determine the peak value. Our findings revealed that force production, activation heat (energy associated with Ca2+ cycling) and cross-bridge heat were unaffected by stimulation frequency. Trabeculae produced greater work output per twitch at 2 Hz and 3.5 Hz than at 5 Hz. Positive correlations among work output, shortening extent and mechanical efficiency were detected. From these findings it was concluded that the higher work output at lower frequencies is associated with greater extent of shortening, which correlates to greater mechanical efficiency. This study highlights the mechano-energetic advantage of ventricular trabeculae in terms of increased work output and energy efficiency gained from operating at lower contraction frequencies, supporting the notion that heart rate reduction produces direct benefits on cardiac energetics.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiological rhythms and metabolic regulation: Shining light on skeletal muscle.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-29 DOI: 10.1113/EP091890

James A Betts, Kelly A Bowden Davies, Harry A Smith, John A Hawley

{"title":"Physiological rhythms and metabolic regulation: Shining light on skeletal muscle.","authors":"James A Betts, Kelly A Bowden Davies, Harry A Smith, John A Hawley","doi":"10.1113/EP091890","DOIUrl":"https://doi.org/10.1113/EP091890","url":null,"abstract":"Metabolic regulation is essential for maintaining homeostasis in response to fluctuating dietary nutrient availability. In this review, we explore how metabolic health can be affected by the temporal alignment between daily behavioural patterns (e.g., eating, physical activity and sleep) and recurring cycles in underlying physiology (e.g., 'circadian' rhythms). Misalignment within and/or between these patterns and cycles can lead to metabolic dysregulation, increasing the risk of chronic disease states such as obesity, type 2 diabetes and cardiovascular disease. Conversely, metabolic health can be improved by strategically aligning certain behavioural patterns with endogenous rhythms in physiology. Dietary interventions based upon this reasoning are referred to as chrono-nutrition strategies. Skeletal muscle is an important tissue in relation to both whole-body metabolism and behaviour and plays a central role in how physiological rhythms respond to the timing of nutrient delivery/availability. Few studies have examined rhythms in metabolism within human skeletal muscle, providing opportunities to advance current understanding of how nutrient timing affects muscle metabolism.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

'Muscular wisdom' revisited: Decaying rates of stimulation mitigate torque loss.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-29 DOI: 10.1113/EP092472

Raaj A Dudani, Alexander M Zero, Charles L Rice

{"title":"'Muscular wisdom' revisited: Decaying rates of stimulation mitigate torque loss.","authors":"Raaj A Dudani, Alexander M Zero, Charles L Rice","doi":"10.1113/EP092472","DOIUrl":"https://doi.org/10.1113/EP092472","url":null,"abstract":"During a sustained high-intensity isometric maximal voluntary contraction (MVC), declining motor unit firing rates (MUFRs) accompany torque loss. This decline (∼50% over 60 s) helps to maintain torque by preserving peripheral electrical propagation and matching the slowing contractile properties with torque loss (i.e., 'muscular wisdom'). However, it has been suggested that reduced MUFRs contribute to torque loss. Here, we compared torque loss between constant and decaying rates of electrical stimulation to mimic MUFRs reported during MVCs. The dorsiflexors of 8 males and 5 females (21-30 years) underwent three 60 s muscle fatiguing conditions: (1) sustained MVC; (2) constant high-frequency electrical stimulation (40 Hz); and (3) exponentially decaying stimulation rate (from 40 to 20 Hz). The decaying rate demonstrated less torque loss compared with the sustained high-frequency stimulation and the MVC conditions (P < 0.01). Furthermore, torque increased (by ∼17%, P < 0.005) when the constant high-frequency condition was switched to 20 Hz for 2 s at task termination. Conversely, torque loss was accelerated when the decaying stimulation rate was switched from 20 to 40 Hz for 2 s at task termination (by ∼16%, P < 0.001). Following all conditions, evoked twitch responses slowed (by 29%-77%, P < 0.01) but M-wave amplitude was reduced only for the constant high-frequency condition (by ∼23%, P < 0.01). Thus, the reduction in stimulation rates maintained optimal activation by matching the fatigue-induced contractile slowing in combination with preserved peripheral electrical conductance. Therefore, reducing the activation rate preserves torque, rather than contributing to torque loss during high-intensity contractions, thereby supporting the muscle wisdom hypothesis.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sedentary lifestyle induces oxidative stress and atrophy in rat skeletal muscle.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-29 DOI: 10.1113/EP092331

Irem Gungor-Orhan, Senay Akin, Scott K Powers, Seda Olgaz-Bingol, Haydar A Demirel

{"title":"Sedentary lifestyle induces oxidative stress and atrophy in rat skeletal muscle.","authors":"Irem Gungor-Orhan, Senay Akin, Scott K Powers, Seda Olgaz-Bingol, Haydar A Demirel","doi":"10.1113/EP092331","DOIUrl":"https://doi.org/10.1113/EP092331","url":null,"abstract":"Abundant evidence indicates that skeletal muscle plays a key role in regulating metabolic homeostasis. Therefore, maintaining healthy skeletal muscles is essential to good health. While prolonged muscle inactivity is known to cause oxidative stress and muscle loss, it remains unclear whether a shift from an active to a sedentary lifestyle induces similar effects. This study tested the hypothesis that transitioning to a sedentary lifestyle rapidly leads to oxidative stress and muscle loss in the load-bearing soleus muscle. Adult Wistar rats were randomly divided into control (CON; n = 8) and sedentary (SED; n = 8) groups. During a 7-day experimental period, CON rats were housed in standard cages allowing free movement, while SED rats were confined to smaller cages promoting sedentary behaviour. Soleus muscles were analysed for antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)), as well as two oxidative stress biomarkers (advanced protein oxidation products (AOPPs) and 4-hydroxynonenal (4-HNE)). Sedentary behaviour caused a 17.2% reduction in the soleus-to-body weight ratio (P < 0.001). Moreover, the activities of SOD, CAT and GPX were significantly lower in the soleus muscle of SED animals (P < 0.05), while AOPPs and 4-HNE levels were higher (P < 0.001 and P < 0.05) compared to CON animals. These findings provide the first evidence that transitioning from an active to a sedentary lifestyle leads to the rapid onset of oxidative stress and atrophy in the soleus muscle. Importantly, the results suggest that impaired antioxidant defences contribute to sedentary behaviour-induced oxidative stress in load-bearing muscles.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paton Prize Lecture Winner 2024: Gordon Holmes and the Irish spirit of adventure: Lessons for modern thinkers.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-28 DOI: 10.1113/EP092192

Seán M Roe

{"title":"Paton Prize Lecture Winner 2024: Gordon Holmes and the Irish spirit of adventure: Lessons for modern thinkers.","authors":"Seán M Roe","doi":"10.1113/EP092192","DOIUrl":"https://doi.org/10.1113/EP092192","url":null,"abstract":"This lecture is given in honour of Sir William Paton (1917-1993), physiologist, pharmacologist and Fellow of the Royal Society. His passion for the history of medicine led to generous donations to the Society, who consequently founded the Paton Prize Fund for historical research. After his death, this eponymous Prize Lecture was debuted in 1994. It has been a singular honour for me to acclaim the similarly influential Irish neurologist Gordon Morgan Holmes (1876-1965), whose work has been a particular preoccupation of mine for my entire career, since I first heard of him as an undergraduate in 1991. Holmes' work on the World War I battlefield completely transformed neurology, in terms both of clinical practice and its knowledge base. Clinical techniques developed by him at that time remain established current practice, and his visual field maps were not superseded for 73 years. His legacy to neurology is extensive, with his editorship of the journal Brain from 1922 to 1937. He had a profound influence both here and across the Atlantic, evinced by global warm tributes published on his death in 1965. The Lecture concentrates on a confluence of events and circumstances existing in the Flanders trenches that met a man singularly suited to overcoming the challenges posed. He received training in neuroanatomy from the German anatomists and clinical skills from the British greats in the National Hospital Queen Square. Coupled with an Irish adventurousness and insatiable curiosity, this experience presaged advances that resonate >100 years on. His legacy speaks profoundly of curiosity, interdisciplinarity and reconciliation.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiology of bridging stent grafts after fenestrated/branched endovascular aortic repair: Where translational science meets the clinical profile.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-27 DOI: 10.1113/EP091813

Thurkga Moothathamby, Matti Jubouri, Tharun Rajasekar, Subham Roy, Maya Alfwaress, Samuel S S Rezk, Samuel N S Ghattas, Mario D'Oria, Damian M Bailey, Ian M Williams, Mohamad Bashir

{"title":"Physiology of bridging stent grafts after fenestrated/branched endovascular aortic repair: Where translational science meets the clinical profile.","authors":"Thurkga Moothathamby, Matti Jubouri, Tharun Rajasekar, Subham Roy, Maya Alfwaress, Samuel S S Rezk, Samuel N S Ghattas, Mario D'Oria, Damian M Bailey, Ian M Williams, Mohamad Bashir","doi":"10.1113/EP091813","DOIUrl":"https://doi.org/10.1113/EP091813","url":null,"abstract":"Fenestrated/branched endovascular aortic repair emerges as the primary therapeutic modality for intricate aortic pathologies encompassing the paravisceral and thoracoabdominal segments, where bridging stent grafts (BSGs) play a vital role in linking the primary aortic endograft with target vessels. Bridging stent grafts can be categorized mainly into self-expanding stent grafts (SESGs) and balloon-expandable stent grafts (BESGs). Physiological factors significantly influence post-complex endovascular aortic repair BSG behaviour, impacting clinical outcomes of SESGs and BESGs in different but overlapping ways. Crucial prerequisites for BSGs encompass not only flexibility but also resilience against mechanical stress and compliance mismatch, especially when bridging the rigid aortic main body with dynamic target vessels. The significance of considering these physiological factors in clinical decision-making is underscored by recognizing the interplay between SESG and BESG characteristics, vessel physiology and patient haemorheology. Such factors include the anatomy and tortuosity of the vessel, diameter of the vessel and BSG, deployment and durability, extrinsic stenosis and respiratory motion. Haemorheological factors, such as anti-thrombotic therapy and hydration status, need to be considered. This narrative review examines both in vitro and in vivo evidence regarding the impact of physiological factors on the behaviour of BSGs and assesses the consequences for clinical outcomes following complex endovascular aortic repair.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In utero exposure to experimental maternal asthma alters fetal airway development in sheep.

IF 2.6 4区医学

Experimental Physiology Pub Date : 2025-01-27 DOI: 10.1113/EP092502

Sarah J Hammond, Andrea J Roff, Joshua L Robinson, Jack R T Darby, Ashley S Meakin, Vicki L Clifton, Robert J Bischof, Michael J Stark, Megan J Wallace, Andrew Tai, Janna L Morrison, Kathryn L Gatford

{"title":"In utero exposure to experimental maternal asthma alters fetal airway development in sheep.","authors":"Sarah J Hammond, Andrea J Roff, Joshua L Robinson, Jack R T Darby, Ashley S Meakin, Vicki L Clifton, Robert J Bischof, Michael J Stark, Megan J Wallace, Andrew Tai, Janna L Morrison, Kathryn L Gatford","doi":"10.1113/EP092502","DOIUrl":"https://doi.org/10.1113/EP092502","url":null,"abstract":"The mechanisms linking maternal asthma (MA) exposure in utero and subsequent risk of asthma in childhood are not fully understood. Pathological airway remodelling, including reticular basement membrane thickening, has been reported in infants and children who go on to develop asthma later in childhood. This suggests altered airway development before birth as a mechanism underlying increased risk of asthma in children exposed in utero to MA. We hypothesised that in utero MA exposure would reduce airway diameter and increase airway-associated smooth muscle area and reticular basement membrane thickness in neonatal offspring. Experimental MA was induced by maternal sensitisation followed by airway challenges with house dust mite before and during pregnancy. Lambs from control (n = 16) or MA (n = 26) ewes were delivered at ∼140 days gestation (term = 150 days), ventilated for 45 min, then humanely killed. Left lungs were inflation-fixed, and cross-sections of generation 2-5 airways were collected. Airway sections were stained with Haematoxylin and Eosin, Masson's Trichrome and Gordon and Sweet's histological stains for morphological analysis. Lamb body and lung weights were similar between groups (P > 0.5 and P > 0.7, respectively). Lambs that were exposed to MA had narrower airway diameters (P = 0.019) and thinner reticular basement membrane (P = 0.016) but similar airway-associated smooth muscle area (P = 0.152) compared with unexposed control lambs. Our results demonstrate a potential mechanism for increased risk of asthma in children of mothers with asthma, independent of genetic risk or behavioural changes during pregnancy.","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0