Journal of Physiology-London最新文献

{"title":"The role of physical exercise in modulating vitamin D metabolite levels: insights and future directions.","authors":"Beatriz de Souza Pitoli, Guilherme Correia Ferri Antonio","doi":"10.1113/JP287724","DOIUrl":"https://doi.org/10.1113/JP287724","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645041","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":"Lactate: a potential brain-targeting exerkine.","authors":"Hash Brown Taha","doi":"10.1113/JP287745","DOIUrl":"https://doi.org/10.1113/JP287745","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640149","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":"Cumulative effects of H⁺ and P_i on force and power of skeletal muscle fibres from young and older adults.","authors":"Christopher W Sundberg, Laura E Teigen, Sandra K Hunter, Robert H Fitts","doi":"10.1113/JP286938","DOIUrl":"https://doi.org/10.1113/JP286938","url":null,"abstract":"<p><p>The cellular causes of the age-related loss in power output and increased fatigability are unresolved. We previously observed that the depressive effects of hydrogen (H⁺) (pH 6.2) and inorganic phosphate (P_i) (30 mm) did not differ in muscle fibres from young and older men. However, the effects may have been saturated in the severe fatigue-mimicking condition, potentially masking age differences in the sensitivity of the cross-bridge to these metabolites. Thus, we compared the contractile mechanics of muscle fibres from the vastus lateralis of 13 young (20-32 years, seven women) and 12 older adults (70-90 years, six women) in conditions mimicking quiescent muscle and a range of elevated H⁺ (pH 6.8-6.6-6.2) and P_i (12-20-30 mm). The older adult knee extensor muscles showed hallmark signs of ageing, including 19% lower thigh lean mass, 60% lower power and a greater fatigability compared to young adult muscles. Progressively increasing concentrations of H⁺ and P_i in the chemically-permeabilized fibre experiments caused a linear decrease in fibre force, velocity and power; however, the effects did not differ with age or sex. Fast fibre cross-sectional area was 41% smaller in older compared to young adults, which corresponded with lower absolute power. Size-specific power was greater in fibres from older compared to young adults, indicating the age-related decline in absolute power was explained by differences in fibre size. These data suggest the age-related loss in power is determined primarily by fast fibre atrophy in men and women, but the age-related increase in fatigability cannot be explained by an increased sensitivity of the cross-bridge to H⁺ and P_i. KEY POINTS: The causes of the age-related loss in muscle power output and the increase in fatigability during dynamic exercise remain elusive. We show that progressively increasing concentrations of hydrogen (H⁺) and inorganic phosphate (P_i) causes a linear decrease in muscle fibre force, velocity and power, but the depressive effects of these metabolites on cross-bridge function did not differ in fibres from older compared to young adults across a range of fatigue-mimicking conditions. We also found peak absolute power did not differ in slow fibres from young and older adults but it was ∼33% lower in older adult fast fibres, which was explained entirely by age differences in fibre size. These data suggest that fast fibre atrophy is a major factor contributing to the loss in power of older men and women, but that the age-related increase in fatigability cannot be explained by an increased sensitivity of the cross-bridge to H⁺ and P_i.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640148","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":"Muscle déjà vu: are myonuclei the blueprint for muscle regrowth?","authors":"Claire Traversa, Alyasamin Alhamwi, Arianne Zabbal, Sarkis Hannaian","doi":"10.1113/JP287606","DOIUrl":"https://doi.org/10.1113/JP287606","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631691","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":"Lack of additional benefit from slow rewarming after therapeutic hypothermia for ischaemic brain injury in near-term fetal sheep.","authors":"Alice McDouall, Kelly Q Zhou, Guido Wassink, Anthony Davies, Laura Bennet, Alistair J Gunn, Joanne O Davidson","doi":"10.1113/JP287453","DOIUrl":"https://doi.org/10.1113/JP287453","url":null,"abstract":"<p><p>The optimal rate of rewarming after therapeutic hypothermia is unclear. Slow rewarming may reduce cardiovascular instability and rebound seizures, but there is little controlled evidence to support this. The present study aimed to determine whether slow rewarming can improve neuroprotection after 72 h of hypothermia. Fetal sheep (0.85 gestation) received sham occlusion (n = 8) or 30 min of global cerebral ischaemia followed by normothermia (n = 7), or hypothermia from 3 to 72 h with either fast, spontaneous rewarming within 1 h (n = 8) or slow rewarming at 0.5°C h^-1 over 10 h (n = 8). Hypothermia improved EEG and spectral edge recovery, with no significant difference between fast and slow rewarming. Hypothermia reduced the number of seizures, with no significant difference in seizure activity between fast and slow rewarming. Hypothermia improved neuronal survival in the cortex, CA1, CA3, CA4 and dentate gyrus regions of the hippocampus, with no significant difference between fast and slow rewarming. Hypothermia attenuated microglia counts in the cortex, with no significant difference between fast and slow rewarming. The rate of rewarming after a clinically relevant duration of hypothermia did not affect neurophysiological recovery, neuronal survival or attenuation of microglia after global cerebral ischaemia in term-equivalent fetal sheep. KEY POINTS: The rate of rewarming after 72 h of hypothermia did not affect recovery of EEG or spectral edge. There was no difference in the occurrence of seizures as a result of the rate of rewarming after hypothermia. The rate of rewarming after 72 h of hypothermia did not affect neuronal survival in the cortex or hippocampus.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631687","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":"Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.","authors":"Cristina Román-Vendrell, Jaqulin N Wallace, Aurelia Hays Watson, Meral Celikag, Tim Bartels, Jennifer R Morgan","doi":"10.1113/JP286281","DOIUrl":"https://doi.org/10.1113/JP286281","url":null,"abstract":"<p><p>Synaptic aggregation of α-synuclein often occurs in Parkinson's disease (PD), dementia with Lewy bodies (DLB) and other synucleinopathies and is associated with cognitive deficits and dementia. Thus, it is important to understand how accumulation of α-synuclein affects synapse structure and function. Native, physiological α-synuclein comprises a mixture of tetramers and related physiological oligomers (60-100 kDa) in equilibrium with monomeric α-synuclein. We previously demonstrated that acutely increasing the levels of physiological α-synuclein impaired intracellular synaptic vesicle trafficking and produced a pleiotropic phenotype, raising questions about which aspects of the synaptic phenotype were due to multimeric versus monomeric α-synuclein. Here, we address this by taking advantage of the unique features of the lamprey giant reticulospinal (RS) synapse, a vertebrate synapse that is amenable to acute perturbations of presynaptic processes via microinjection of purified proteins. α-Synuclein monomers and multimers were purified from HEK cells and separately introduced to lamprey synapses. Ultrastructural analysis revealed that both multimeric and monomeric α-synuclein impaired intracellular vesicle trafficking, leading to a loss of synaptic vesicles and buildup of endosomes. However, while monomeric α-synuclein additionally induced atypical fusion/fission at the active zone and impaired clathrin-mediated endocytosis, multimeric α-synuclein did not. Conversely, multimeric α-synuclein led to a decrease in synaptic vesicle docking, which was not observed with monomeric α-synuclein. These data provide further evidence that different molecular species of α-synuclein produce distinct and complex impacts on synaptic vesicle trafficking and reveal important insights into the cell biological processes that are affected in PD and DLB. KEY POINTS: α-Synuclein accumulation at synapses is associated with cognitive decline and dementia in Parkinson's disease and other synucleinopathies. We previously showed that acute introduction of excess human brain-derived α-synuclein to lamprey giant synapses caused pleiotropic phenotypes on synaptic vesicle trafficking, probably due to the mixture of molecular species of α-synuclein. Here, we dissected which aspects of the synaptic phenotypes were caused by monomeric (14 kDa) or multimeric (60-100 kDa) α-synuclein by purifying each molecular species and introducing each one separately to synapses via axonal microinjection. While monomeric α-synuclein inhibited clathrin-mediated synaptic vesicle endocytosis, multimeric α-synuclein primarily impaired endosomal trafficking. These findings reveal that different molecular species of α-synuclein have distinct impacts on synapses, suggesting different cellular and molecular targets.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631656","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":"Calcium flux balance in the heart: how many of the important questions are really unanswered?","authors":"David A Eisner, David J Greensmith, Andrew W Trafford","doi":"10.1113/JP287849","DOIUrl":"https://doi.org/10.1113/JP287849","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631660","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":"Exposing mice to extremely hypertonic treatments: a recurring problem in lactate research.","authors":"Jens Lund, Zachary Gerhart-Hines, Christoffer Clemmensen","doi":"10.1113/JP287781","DOIUrl":"https://doi.org/10.1113/JP287781","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631675","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":"Critical closing pressure and resistance-area product as markers of cerebral autoregulation dynamics.","authors":"Stephen Payne","doi":"10.1113/JP287876","DOIUrl":"https://doi.org/10.1113/JP287876","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631665","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":"Interleukin-1β signalling in muscle atrophy: linking inflammation, sex-specific responses and exercise in cancer cachexia.","authors":"Vito A Pipitone, Mackenzie Q Graham, Lauren S Perkins, Daniel L Scurto, Jacob M Ouellette, Fasih A Rahman","doi":"10.1113/JP287733","DOIUrl":"https://doi.org/10.1113/JP287733","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631681","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}