Journal of Physiology-London最新文献

{"title":"Endurance exercise selectively elevates mBDNF across age groups in humans.","authors":"Aaron Wang, Ryan Dang, Nicole Adara Case, Bilal F Hamzeh","doi":"10.1113/JP289010","DOIUrl":"https://doi.org/10.1113/JP289010","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A computational model of age-dependent cardiomyocyte apoptosis.","authors":"Elena Kutumova, Ilya Kiselev, Fedor Kolpakov","doi":"10.1113/JP288853","DOIUrl":"https://doi.org/10.1113/JP288853","url":null,"abstract":"<p><p>Hypertension and ageing are risk factors for arterial stiffness, which increases cardiac overload and causes left ventricular (LV) hypertrophy. Cardiomyocyte apoptosis acts as a regulatory mechanism that participates in the adaptive response of the heart to pressure overload. Anti-hypertensive drugs can exert anti-apoptotic effects on cardiomyocytes, which are important therapeutic targets for cardio protection. The angiotensin II receptor blocker losartan, used in hypertension and cardiac remodelling, may inhibit cardiomyocyte apoptosis, possibly by reducing Bax expression. To study the effect of apoptotic signals in LV myocytes on patient survival with and without losartan treatment we used a previously developed mathematical model of the human cardiovascular and renal systems. Here we extended this model to include mechanisms of CD95-induced cardiomyocyte apoptosis. Our model is the first to integrate a mechanistic view of cardiorenal processes with biochemical mechanisms of cell death. The model predicted that therapeutic intervention on cardiac apoptotic pathways could significantly improve the survival in patients with cardiac pressure overload pathology. Although the modelling results showed that losartan suppresses cardiomyocyte apoptosis primarily through its effects on LV haemodynamic function, the model demonstrated that in diseases that promote water and sodium accumulation in the body, the therapeutic effect of losartan on molecular apoptotic processes may be more significant than its effects on LV haemodynamics. KEY POINTS: Therapeutic interventions that target cardiac apoptotic pathways have the potential to markedly improve the survival of patients with cardiac pressure overload pathology. The findings of the modelling suggest that losartan suppresses cardiomyocyte apoptosis primarily through its effect on left ventricular haemodynamic function. In diseases that result in the accumulation of water and sodium within the body the therapeutic efficacy of losartan on molecular apoptotic processes may prove to be more significant than its effects on left ventricular haemodynamics.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral blood flow with exogenous ketosis: The full picture?","authors":"Myrthe Stalmans, Chiel Poffé","doi":"10.1113/JP289386","DOIUrl":"https://doi.org/10.1113/JP289386","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the interplay of hepatic ketogenesis, mitochondrial function and endurance exercise in cognitive health amidst ageing.","authors":"Yu-Hsiang Lin, Chien-Lun Chen, Jau-Yuan Chen","doi":"10.1113/JP289328","DOIUrl":"https://doi.org/10.1113/JP289328","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial phagocytosis in epilepsy: Mechanisms and impact.","authors":"Abhijeet S Barath, Long-Jun Wu","doi":"10.1113/JP288573","DOIUrl":"https://doi.org/10.1113/JP288573","url":null,"abstract":"<p><p>Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non-inflammatory cell death. This process involves a range of well-characterized 'find me' and 'eat me' signals, phagocytic receptors, and less well-characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of developing spontaneous recurrent seizures. Reconciling these dual effects requires a deeper understanding the spatiotemporal dynamics of microglial phagocytosis. The objective of this review is to examine the mechanisms and impact of microglial phagocytosis in the context of epilepsy and to highlight unresolved questions that warrant further investigation in this emerging field.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The stretch-shortening cycle effect is not associated with cortical or spinal excitability modulations.","authors":"Lea-Fedia Rissmann, Brent James Raiteri, Wolfgang Seiberl, Tobias Siebert, Daniel Hahn","doi":"10.1113/JP287508","DOIUrl":"https://doi.org/10.1113/JP287508","url":null,"abstract":"<p><p>It is unclear whether cortical and spinal excitability modulations contribute to enhanced stretch-shortening cycle (SSC) performance. Therefore, this study investigated cortical and spinal excitability modulations during and following shortening of SSC contractions compared with pure shortening (SHO) contractions. Participants (n = 18) performed submaximal voluntary plantar flexion contractions while prone on the dynamometer bench. The right foot was strapped onto the dynamometer's footplate attachment, and the resultant ankle joint torque and crank arm angle were recorded. Cortical and spinal excitability modulations of the soleus muscle were analysed by eliciting compound muscle actional potentials via electrical nerve stimulation, cervicomedullary motor-evoked potentials (CMEPs) via electrical stimulation of the spinal cord, and motor-evoked potentials (MEPs) via magnetic stimulation of the motor cortex. Mean torque following stretch was significantly increased by 7 ± 3% (P = 0.029) compared with the fixed-end reference (REF) contraction, and mean torque during shortening of SSC compared with SHO was significantly increased by 12 ± 24% (P = 0.046). Mean steady-state torque was significantly lower by 13 ± 3% (P = 0.006) and 9 ± 12% (P = 0.011) following SSC compared with REF and SHO, respectively. Mean steady-state torque was not significantly different following SHO compared with REF (7 ± 8%, P = 0.456). CMEPs and MEPs were also not significantly different during shortening of SSC compared with SHO (P ≥ 0.885) or during the steady state of SSC, SHO and REF (P ≥ 0.727). Therefore, our results indicate that SSC performance was not associated with cortical or spinal excitability modulations during or after shortening, but rather driven by mechanical mechanisms triggered during active stretch. KEY POINTS: A stretch-shortening cycle (SSC) effect of 12% was observed during EMG-matched submaximal voluntary contractions of the human plantar flexors. The SSC effect was neither associated with cortical or spinal excitability modulations nor with stretch-reflex activity. The SSC effect was likely driven by mechanical mechanisms related to active muscle stretch, which have long-lasting effects during shortening. Residual force depression following SSC was not attenuated by the long-lasting mechanical mechanisms triggered during active muscle stretch. Steady-state torques were lower following shortening of SSCs versus pure shortening and fixed-end contractions at the same final ankle joint angle, but the torque differences were not correlated with cortical or spinal excitability modulations.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Running toward brain health: How aerobic capacity and liver metabolism shape Alzheimer's pathology.","authors":"Evelin Melekh, Madeleine King, Julia G Stante, Emma L Cook, Grace Sargeant, Sarah Bellaflor","doi":"10.1113/JP289269","DOIUrl":"https://doi.org/10.1113/JP289269","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obligatory and accessory respiratory muscle structure, function and control in early and advanced disease in the mdx mouse model of Duchenne muscular dystrophy.","authors":"Aoife D Slyne, David P Burns, Karina Wöller, Amandine May, Roisin Dowd, Sarah E Drummond, Grzegorz Jasionek, Ken D O'Halloran","doi":"10.1113/JP288709","DOIUrl":"https://doi.org/10.1113/JP288709","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Peak inspiratory pressure-generating capacity is preserved in the mdx mouse model of Duchenne muscular dystrophy in early disease, despite profound diaphragm muscle weakness and reduced electrical activation, revealing adequate compensation by extra-diaphragmatic muscles. Respiratory system compensation is lost as disease progresses, with the emergence of reduced peak inspiratory pressure-generating capacity in advanced disease. We hypothesised that extra-diaphragmatic inspiratory muscles compensate for diaphragm dysfunction in early dystrophic disease, supporting the maintenance of peak respiratory performance in mdx mice. We reasoned that extra-diaphragmatic muscle dysfunction would emerge with progressive disease, leading to the loss of peak inspiratory pressure-generating capacity in advanced dystrophic disease. We measured ventilation, inspiratory pressure, and obligatory (diaphragm, intercostal and parasternal) and accessory (sternomastoid, cleidomastoid, scalene and trapezius) respiratory muscle form, function and EMG activity in early (4 months) and advanced (16 months) dystrophic disease. Despite obligatory and accessory muscle dysfunction, including structural remodelling, weakness and reduced EMG activity, peak inspiratory pressure-generating capacity and ventilation are preserved in early disease. Obligatory and accessory muscle dysfunction progressively declines with advanced disease, with the emergence of reduced peak inspiratory pressure-generating capacity. However, although there was evidence of progressive accessory muscle dysfunction, more profound remodelling was seen in the diaphragm muscle comparing early and advanced dystrophic disease. In conclusion, in early dystrophic disease, peak inspiratory performance is compensated. A progressive decline in diaphragm and extra-diaphragmatic muscles contributes to respiratory system compromise in advanced disease. Further loss of compensation afforded by extra-diaphragmatic muscles probably contributes to end-stage respiratory failure. KEY POINTS: We characterised obligatory and accessory respiratory muscle form, function and control in early and advanced disease in the mdx mouse model of Duchenne muscular dystrophy. Profound diaphragm muscle remodelling, immune cell infiltration, elevated cytokine concentrations and dysfunction present in early disease, but peak inspiratory performance is fully compensated. The burden of breathing is shared across many muscles, revealed as remodelling, elevated cytokine concentrations, weakness and impaired control in several obligatory and accessory muscles. Peak inspiratory performance declines in advanced disease with evidence of progressive remodelling in the diaphragm muscle with extensive fibrosis and further decline in the form, function and control of accessory muscles of breathing. Diaphragm remodelling with profound fibrosis, more so than progressive accessory muscle remodelling (although evident), is the striking phenotype at 16 mon","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From reflex to relief: modifying the muscle metaboreflex in heart failure.","authors":"Seth W Holwerda","doi":"10.1113/JP289154","DOIUrl":"https://doi.org/10.1113/JP289154","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local and global control on mitochondrial ageing.","authors":"Luigi Ferrucci, Natalia Bobba-Alves, David J Marcinek","doi":"10.1113/JP289058","DOIUrl":"https://doi.org/10.1113/JP289058","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}