{"title":"Exercise-induced signalling in alleviating neuronal insulin resistance.","authors":"Ishitha Reddy, Chinmoy Sankar Dey","doi":"10.1113/JP287750","DOIUrl":"https://doi.org/10.1113/JP287750","url":null,"abstract":"<p><p>Exercise contributes to a multitude of positive changes within the body and brain with regard to glucose homeostasis, insulin sensitivity, synaptic plasticity, neuroprotection and neurogenesis, among other effects. It provides a non-pharmaceutical alternative for addressing metabolic disorders in individuals with type 2 diabetes, who also face an increased risk of developing Alzheimer's disease. A number of molecules are evoked upon exercise and circulate through the bloodstream, transmitting the wide-reaching advantages of exercise. The ensuing cross-talk has been shown to improve conditions associated with Alzheimer's disease. The vast signalling network mediated by exercise is currently being studied extensively and its implications in improving neuronal insulin resistance, especially as a bypass mechanism, are of major interest. Taking into account sirtuin 1/peroxisome proliferator-activated receptor γ co-activator 1-α, AMP-activated protein kinase, phosphoinositide 3-kinase/AKT, phospholipase C-γ and brain-derived neurotrophic factor/tropomyosin receptor kinase B among many pathways and cross-interactions involved, researching the molecular characteristics of brain exercise signalling and the mechanisms by which it compensates for hampered signalling is crucial for future research.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773960","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":"Melatonin: a lifeline for cardiac dysfunction in hypoxic pregnancy","authors":"Salman Ahmad","doi":"10.1113/JP288323","DOIUrl":"10.1113/JP288323","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 9","pages":"2477-2479"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755549","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}
Sebastian Edman, Julia Starck, Linnéa Corell, William Hangasjärvi, Amelie von Finckenstein, Mikael Reimeringer, Stefan Reitzner, Jessica Norrbom, Marcus Moberg, Ferdinand von Walden
{"title":"Exercise-induced plasma mature brain-derived neurotrophic factor elevation in children, adolescents and adults: influence of age, maturity and physical activity","authors":"Sebastian Edman, Julia Starck, Linnéa Corell, William Hangasjärvi, Amelie von Finckenstein, Mikael Reimeringer, Stefan Reitzner, Jessica Norrbom, Marcus Moberg, Ferdinand von Walden","doi":"10.1113/JP288170","DOIUrl":"10.1113/JP288170","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a central role in neuronal health. BDNF exists in two primary isoforms, the mature form (mBDNF) and its precursor (proBDNF), with opposing downstream effects on neuronal function. The positive effect of exercise on plasma levels of the BDNF isoforms has been extensively studied in adults. However, equivalent investigations are lacking in children and adolescents. Twenty healthy children (9–12 years old), 19 adolescents (13–17 years old) and 39 adults (23–49 years old) donated venous blood before and after a 45-minute run. Platelet-poor plasma was analysed for pro- and mBDNF using an enzyme-linked immunosorbent assay. Maximal oxygen uptake and anthropometric data were assessed in all participants, while Tanner stage, circulating sex hormones and accelerometry-based activity level were assessed in children and adolescents only. We found that children, adolescents and adults have similar circulating levels of plasma pro- and mBDNF at rest. For children and adolescents, resting levels of mBDNF correlated with average time spent in vigorous activity. In response to the acute endurance exercise intervention, mBDNF increased in all age groups, but the greatest rise in mBDNF was seen in adults. The acute endurance exercise did not affect proBDNF levels. Our results demonstrate that plasma mBDNF levels, but not proBDNF, increase following endurance exercise in all age groups, with a greater effect in adults. We also show that high-intensity physical activity, but not underlying fitness, is contributing to sustained elevated mBDNF levels.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We show that in children and adolescents, regular vigorous physical activity is key to increased basal levels of plasma mature brain-derived neurotrophic factor (mBDNF), a factor linked to neuroplasticity and brain health.</li>\u0000 \u0000 <li>The ability to elevate mBDNF through exercise is present across all age groups, with the greatest increase in adults.</li>\u0000 \u0000 <li>The mBDNF response to physical exercise seems to be independent of underlying physical fitness.</li>\u0000 \u0000 <li>Our findings suggest that basal plasma mBDNF levels may reflect the cumulative effects of repeated exercise rather than an individual's overall physical fitness.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 8","pages":"2333-2347"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP288170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effects of local vibration inducing a tonic vibration reflex or movement illusion on acute modulations of corticospinal excitability","authors":"Nicolas Amiez, Alain Martin, Christos Paizis","doi":"10.1113/JP286689","DOIUrl":"10.1113/JP286689","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Stimulation of muscle afferents by local vibration (LV) can lead to two distinct perceptual and motor responses: the tonic vibration reflex (TVR) or the movement illusion. This study aimed to evaluate the effect of TVR and movement illusion on corticospinal excitability. In two experiments, EMG activity of the vibrated flexor carpi radialis (FCR) muscle (80 Hz, 6 min) and the extensor carpi radialis (ECR) muscle were recorded. Illusion was assessed using questionnaires. LV conditions were adjusted to favour either TVR (visual attention focused on the vibrating wrist) or ILLUSION (hidden hand, visual attention focused on the EMG of the FCR muscle). Motor-evoked potential (MEP) and cervicomedullary motor-evoked potential (CMEP) were recorded at rest for both muscles before (10 and 0 min) and after (0 and 30 min) each LV condition. Only the TVR condition increased EMG of the FCR muscle (+490% compared to resting, <i>P</i> = 0.005), while movement illusion was greater in the ILLUSION condition (<i>P </i>< 0.001). Concerning the vibrated muscle at P0, TVR reduced the amplitude of CMEP (−13.8 ± 15.8%, <i>P</i> = 0.011) without altering MEP (0.3 ± 27.9%, <i>P</i> = 1), whereas the opposite occurred with movement illusion (i.e. CMEP: −4.5 ± 13.7%, <i>P</i> = 0.891; MEP: −25.1 ± 17.2%, <i>P</i> = 0.002). Cortical excitability (MEP/CMEP ratio) of the vibrated muscle was reduced by 24 ± 13.3% on average compared to values obtained before LV, only in the ILLUSION condition. In conclusion, this study highlights the relevance of measuring and reporting the perceptual and motor responses induced during LV, demonstrating that TVR and movement illusion partly determine the acute effects on the neural network.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Tonic vibration reflex and movement illusion are rarely controlled and measured in studies investigating the effect of LV on corticospinal excitability.</li>\u0000 \u0000 <li>The application of LV with visual attention focused on the vibrated muscle promotes the presence of a tonic vibration reflex (TVR). The absence of visual feedback on the latter promotes the presence of an illusion of movement.</li>\u0000 \u0000 <li>The cortical excitability of the vibrated muscle is influenced differently according to the perceptual and motor responses induced during LV, with an opposite effect on the cortical excitability of the antagonist muscle.</li>\u0000 \u0000 <l","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 9","pages":"2741-2762"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP286689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuron–non-neuron electrical coupling networks are involved in chronic stress-induced electrophysiological changes in lateral habenular neurons","authors":"Kenji Yamaoka, Kanako Nozaki, Meina Zhu, Haruhi Terai, Kenta Kobayashi, Hikaru Ito, Miho Matsumata, Hidenori Takemoto, Shinya Ikeda, Yusuke Sotomaru, Tetsuji Mori, Hidenori Aizawa, Kouichi Hashimoto","doi":"10.1113/JP287286","DOIUrl":"10.1113/JP287286","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>The lateral habenula (LHb) is a key brain structure that receives input from higher brain regions and regulates monoaminergic activity. LHb hyperactivity has been implicated in the pathophysiology of depression, but the electrophysiological mechanisms underlying this hyperactivity remain poorly understood. To address this issue, we investigated how chronic stress alters the firing properties of LHb neurons in a mouse model of chronic social defeat. Whole-cell recordings were conducted from LHb neurons in the mouse acute brain slices. LHb neurons exhibited two types of rebound depolarizing potentials (RDPs) after the offset of hyperpolarization: short-RDPs (lasting <400 ms) and long-RDPs (order of seconds). Stress-susceptible mice showed a significantly reduced occurrence of long-RDPs, whereas spike firing in response to depolarizing current injections remained unchanged. Both short- and long-RDPs were triggered by T-type voltage-dependent Ca<sup>2+</sup> channels and shortened by small-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (SK) channels. The prolonged depolarizing phase of long-RDPs was mediated by cyclic nucleotide-gated (CNG) channels, which were activated via electrical coupling formed between neurons and non-neuronal cells. Whole-cell recording using an internal solution including a gap junction-permeable dye revealed that neurons formed dye coupling with non-neuronal cells, including oligodendrocytes and/or oligodendrocyte precursor cells. RNA-sequencing and genome editing experiments suggested that <i>Cnga4</i>, a CNG channel subtype, was the primary candidate for the long depolarizing phase of long-RDP, and its expression was decreased in the stress-susceptible mice. These findings suggest that stress-dependent changes in the firing activity of neurons are regulated by neuron–non-neuron networks formed in the LHb.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Mouse lateral habenular (LHb) neurons exhibit short (<400 ms) rebound depolarizing potentials (short-RDPs) or long-RDPs (order of seconds) (long-RDPs) after the offset of hyperpolarization.</li>\u0000 \u0000 <li>The incidence of long-RDP neurons is significantly reduced in mice susceptible to chronic social defeat stress.</li>\u0000 \u0000 <li>The long depolarizing phase of long-RDPs is mediated by cyclic nucleotide-gated (CNG) channels, which are activated in non-neuronal cells via gap junctions.</li>\u0000 \u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 9","pages":"2713-2740"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eduardo Colombari, Vinícia Campana Biancardi, Débora Simões Almeida Colombari, Pedro Lourenço Katayama, Fernanda de Campos de Medeiros, Andrew Vieira Aitken, Carlos Henrique Xavier, Gustavo Rodrigues Pedrino, Denis E. Bragin
{"title":"Hypertension, blood–brain barrier disruption and changes in intracranial pressure","authors":"Eduardo Colombari, Vinícia Campana Biancardi, Débora Simões Almeida Colombari, Pedro Lourenço Katayama, Fernanda de Campos de Medeiros, Andrew Vieira Aitken, Carlos Henrique Xavier, Gustavo Rodrigues Pedrino, Denis E. Bragin","doi":"10.1113/JP285058","DOIUrl":"10.1113/JP285058","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Intracranial pressure (ICP) is pressure within the cranium, between 5 and 15 mmHg in a normal brain, and is influenced by the dynamic balance between brain tissue, cerebrospinal fluid (CSF) and cerebral blood volume. ICP is vital for cerebral health, impacting outcomes in various neurological conditions. Disruptions, such as cerebral haemorrhage, hydrocephalus and malignant hypertension, can lead to elevated ICP, a dangerous condition known as intracranial hypertension (IH). Systemic hypertension significantly impacts cerebral health by causing microvascular damage, dysfunction of the blood–brain barrier (BBB) and impairment of intracranial compliance (ICC). This increases the risk of IH), cerebral ischaemia, neuroinflammation and lacunar infarction, further worsening neurological dysfunction. This review describes the complex relationship between hypertension and ICP regulation, focusing on the mechanisms underlying ICP and ICC adjustments in hypertensive conditions and emphasizing the role of BBB integrity and cerebral blood flow (CBF) dynamics. It discusses how the sympathetic output might change the regulation of CBF and the maintenance of ICP, highlighting how hypertensive conditions can impair this mechanism, increasing the risk of cerebral ischaemia. The neurovascular unit, including astrocytes and microglia, plays a significant role in this process, contributing to IH in hypertensive patients. Understanding the effects of hypertension on ICP and ICC could lead to therapies aimed at preserving BBB integrity, reducing inflammation and improving cerebral compliance, potentially preventing brain dysfunction and reducing stroke risk in hypertensive patients. This review underscores the need for early detection and intervention to mitigate the severe consequences of uncontrolled hypertension on cerebral health.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 8","pages":"2245-2261"},"PeriodicalIF":4.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP285058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sergiy Klid, Francisco Algaba-Chueca, Elsa Maymó-Masip, Mónica Ballesteros, Montse Inglés, Albert Guarque, Nerea Vilanova-Ricart, Ariadna Prats, Azra Kulovic-Sissawo, Elisa Weiss, Ursula Hiden, Joan Vendrell, Sonia Fernández-Veledo, Ana Megía
{"title":"Impaired angiogenesis in gestational diabetes is linked to succinate/SUCNR1 axis dysregulation in late gestation.","authors":"Sergiy Klid, Francisco Algaba-Chueca, Elsa Maymó-Masip, Mónica Ballesteros, Montse Inglés, Albert Guarque, Nerea Vilanova-Ricart, Ariadna Prats, Azra Kulovic-Sissawo, Elisa Weiss, Ursula Hiden, Joan Vendrell, Sonia Fernández-Veledo, Ana Megía","doi":"10.1113/JP288010","DOIUrl":"https://doi.org/10.1113/JP288010","url":null,"abstract":"<p><p>Recent research has highlighted the significance of succinate and its receptor in gestational diabetes (GDM) pathogenesis. However, a clear interconnection between placenta metabolism, succinate levels, SUCNR1 signalling and pregnancy pathologies remains elusive. Here, we set out to investigate the potential role of succinate on labour and placental mechanisms by combining clinical and functional experimental data at the same time as exploring the specific SUCNR1-mediated effects of succinate on placenta vascularization, addressing its specific agonist actions. According to our data, succinate levels vary throughout pregnancy and postpartum, with a natural increase during the peripartum period. We also show that SUCNR1 activation in the umbilical cord endothelium promotes angiogenesis under normal conditions. However, in GDM, excessive succinate and impaired SUCNR1 function may weaken this angiogenic response. In conclusion, the present study underlines succinate as an emerging signalling molecule in the placenta, regulating labour and placental processes. The reduced sensitivity of the succinate/SUCNR1 pathway in the GDM environment may serve as a protective physiological mechanism or could have a pathogenic effect. KEY POINTS: Succinate levels increase at delivery in maternal and fetal circulation. Gestational diabetes (GDM) induces succinate accumulation and SUCNR1 downregulation in umbilical cords. GDM compromises angiogenic gene profile modulation by SUCNR1 in umbilical cord endothelium. SUCNR1 activation stimulates sprouting and tube-forming capacity of human umbilical vein endothelial cells from healthy, but not GDM pregnancies.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755318","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}
Jochen Zange, Joachim Endres, Christoph S Clemen, Jörn Rittweger
{"title":"Leg and hip muscles show muscle-specific effects of ageing and sport on muscle volume and fat fraction in male Masters athletes.","authors":"Jochen Zange, Joachim Endres, Christoph S Clemen, Jörn Rittweger","doi":"10.1113/JP285665","DOIUrl":"https://doi.org/10.1113/JP285665","url":null,"abstract":"<p><p>Age-related deterioration in muscle volume, intramuscular fat content and muscle function can be modulated by physical activity. We explored whether Masters athletes, as examples of highly physically active people into old age, could prevent these age-related muscle deteriorations. Four groups of 43 men were examined: young athletes (20-35 years, n = 10), Masters athletes (60-75 years, n = 10) and two age-matched control groups (old: n = 11, young: n = 12). Volumes and fat fractions of 17 different hip and leg muscles were determined using magnetic resonance imaging. In the soleus muscle extra- and intramyocellular lipids were measured using 1H-MR-spectroscopy. Finally volumes of glutei, quadriceps and triceps surae muscles were cumulated and compared to peak jumping power. In both age groups the sum of glutei, quadriceps and triceps surae muscles showed larger volumes in athletes (young: 5758 ± 1139 ml, old: 5285 ± 895 ml) compared to the corresponding control groups (young: 4781 ± 833 ml, old: 4379 ± 612 ml) (p < 0.001). Fat fraction varied between 1.5% and 12.5% <sup>1</sup>H-signal across muscles and groups and was greater in Masters athletes than in young athletes (p < 0.001), but lower than that in old controls (p < 0.001) and comparable with young controls. Age and exercise-related effects on muscle fat predominantly originated from the extramyocellular lipids. Finally muscle peak power per volume was effectively halved in the combined older groups compared to the younger groups. Our findings suggest that sarcosthenia, that is, intrinsic muscle weakness, is an effective cause of age-related power declines in addition to sarcopenia and fat accumulation. KEY POINTS: Muscle volume and muscle fat fraction from 17 hip and leg muscles of Masters athletes were compared with old controls, young athletes and young controls. Muscle volume and fat fraction were determined using magnetic resonance imaging (MRI) using a six-point-DIXON sequence. Muscle volume in Masters athletes was larger than that in old controls but partially smaller than that in young athletes. Muscle fat fraction of Masters athletes was lower than that in old controls but higher than that in young athletes. Muscles of old athletes and old controls produce only 50% of jumping peak power per muscle volume compared with younger subjects. The intrinsic reduction of power loss in old muscle could not be explained by the higher fat fraction in old muscle.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755515","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}
Jonas Rud Bjørndal, Lasse Jespersen, Mikkel Malling Beck, Anke Ninija Karabanov, Lasse Christiansen, Jesper Lundbye-Jensen
{"title":"Paired corticospinal-motoneuronal stimulation enhances ballistic motor learning and corticospinal plasticity in older adults.","authors":"Jonas Rud Bjørndal, Lasse Jespersen, Mikkel Malling Beck, Anke Ninija Karabanov, Lasse Christiansen, Jesper Lundbye-Jensen","doi":"10.1113/JP287204","DOIUrl":"https://doi.org/10.1113/JP287204","url":null,"abstract":"<p><p>Late adulthood is accompanied by declines in manual motor performance and reduced neuroplasticity, which can influence the effects of motor practice and learning. Corticomotoneuronal (CM) connectivity can be targeted non-invasively through individualized paired corticospinal-motoneuronal stimulation (PCMS) to prime ballistic motor learning in young adults. However, the priming effects of PCMS on motor output and ballistic motor learning in older adults remain unexplored. Part one of this study investigates ballistic motor performance and learning in young (20-30 years) and older (65-75 years) adults as within-session changes in peak acceleration of rapid index finger flexions and delayed retention 1 week later. The results demonstrate that older adults display lower maximal acceleration compared to young adults and smaller improvements with practice, indicating inferior learning and low levels of delayed retention. Part two of the study investigates the effects of PCMS on motor learning and corticospinal excitability in older adults. Corticospinal excitability was assessed throughout the experiment by recording motor evoked potentials from the first dorsal interosseous. PCMS increased subsequent ballistic learning and corticospinal excitability after practice compared to SHAM. Importantly, combined PCMS and motor practice also enhanced long-term retention, and performance remained enhanced 7 days later. This means that PCMS effectively reinstated the otherwise absent long-term learning in older adults. We demonstrate that PCMS primes experience-dependent plasticity accompanying motor learning resulting in long-term benefits on motor performance in older adults. These findings highlight the potential of PCMS to enhance the effects of motor practice and benefit functional abilities in older adults. KEY POINTS: Late adulthood is associated with reduced activation of spinal motoneurons during vigorous movements, resulting in slower and less precise movements. Older adults (aged 65-75 years) display lower ballistic motor performance compared to younger adults (aged 20-30 years); furthermore, older adults exhibit smaller improvements during practice, and lower retention. A single session of paired corticospinal-motoneuronal stimulation (PCMS) increases corticospinal excitability and primes within-session ballistic motor learning in older adults. A single session of PCMS improves long-term retention following ballistic motor learning. We provide proof-of-principle that PCMS represents a potential strategy to enhance the effects of motor practice and counteract age-related decline in motor function.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755552","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}
Thomas Hinton, Katrina Hope, Zoe Adams, Lydia L. Simpson, Julian F. R. Paton, Adrian Kendrick, Ana P. Abdala, Hazel Blythe, Angus K. Nightingale, Emma C. Hart
{"title":"Carotid chemoreflex control of blood pressure at rest and during exercise in young-onset hypertension","authors":"Thomas Hinton, Katrina Hope, Zoe Adams, Lydia L. Simpson, Julian F. R. Paton, Adrian Kendrick, Ana P. Abdala, Hazel Blythe, Angus K. Nightingale, Emma C. Hart","doi":"10.1113/JP287743","DOIUrl":"10.1113/JP287743","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Despite reports of amplified carotid chemoreflex sensitivity to hypoxia in young adults with hypertension (<40 years), it is unclear whether this equates to a direct role of this reflex in maintaining high resting and exercise blood pressures (BP). The aim of this study was to examine whether tonic carotid chemoreflex activity contributes to high resting and exercise BP in young people with untreated hypertension compared to normotensives (NTN). In 14 NTN and 14 untreated hypertensives (HTN) (aged 27 ± 6 and 28 ± 5 years, respectively) the ventilatory and haemodynamic responses to hypoxia were measured using the transient hypoxic test at rest and during submaximal steady-state upright cycle exercise (40%–50% <span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <mrow>\u0000 <msub>\u0000 <mi>O</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 <mi>peak</mi>\u0000 </mrow>\u0000 </msub>\u0000 <annotation>${dot V_{{{mathrm{O}}_2}{mathrm{peak}}}}$</annotation>\u0000 </semantics></math>). A double-blinded placebo-controlled systemic infusion of low-dose dopamine (2 mcg/kg/min) was used to inhibit the carotid chemoreflex and assess its tonic contribution to ventilation and BP at rest and submaximal exercise (mixed-model ANOVA). The hypoxic ventilatory response (HVR) at rest and submaximal cycle exercise were comparable between groups and were similarly blunted by dopamine infusion in both groups. However, at rest, there was a greater decrease in resting systolic BP (SBP) during carotid chemoreflex inhibition in the HTN group. Notably, during submaximal exercise, SBP was reduced during dopamine <i>versus</i> that during saline, but the decrease was similar between groups. The carotid chemoreflex appears to contribute to resting SBP in young people with untreated HTN but does not play a role in exaggerated exercise BP responses in this group.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The role of the carotid chemoreflex in maintaining high resting and exercise blood pressures in young adults with untreated hypertension is unclear.</li>\u0000 \u0000 <li>Carotid che","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 8","pages":"2313-2332"},"PeriodicalIF":4.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}