Experimental Physiology最新文献

{"title":"Unveiling the role of melatonin-related gene CSNK1D in osteoclastogenesis and its implications for osteoporosis treatment","authors":"Jiewen Zhang,&nbsp;Shaobo Wu,&nbsp;Fangze Xing,&nbsp;Ning Kong,&nbsp;Yiwei Zhao,&nbsp;Xudong Duan,&nbsp;Yiyang Li,&nbsp;Kunzheng Wang,&nbsp;Run Tian,&nbsp;Pei Yang","doi":"10.1113/EP092189","DOIUrl":"10.1113/EP092189","url":null,"abstract":"<p>Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone density and quality, increasing fragility and fracture risk. Osteoclast (OC) activity and circadian rhythm play a role in the pathogenesis of OP. Melatonin is a circadian regulator that affects bone metabolism, but its molecular mechanism has not been studied in detail. This study aimed to identify the relationship between melatonin-related genes and OP through bioinformatics methods and to verify it experimentally.We analysed microarray data from the GSE35959 dataset, identifying differentially expressed genes in OP patients. Circadian rhythm-related genes and melatonin-related genes intersect with these differentially expressed genes, highlighting that <i>CSNK1D</i> is a central gene. Functional enrichment, correlation and protein–protein interaction analyses were conducted. Experimental validation involved in vitro differentiation assays using RAW264.7 cells and in vivo studies with an ovariectomy-induced rat model of OP to evaluate the role of <i>CSNK1D</i> in osteoclastogenesis to verify its effect on OP. Differential expression analysis revealed 272 significant genes, with <i>CSNK1D</i> identified as central to the circadian rhythm and to melatonin and OP interplay. Functional analyses showed involvement of <i>CSNK1D</i> in OC differentiation and inflammatory pathways. in vitro experiments confirmed <i>CSNK1D</i> upregulation during OC differentiation, and small interfering RNA-mediated knockdown reduced OC marker expression and TRAP⁺ cell formation. in vivo, <i>CSNK1D</i> expression is associated with bone loss in OP rats. Melatonin-related <i>CSNK1D</i> promotes OC differentiation and promotes the development of OP. These findings suggest <i>CSNK1D</i> as a potential therapeutic target for OP, offering insights into new treatment strategies integrating circadian rhythm regulation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 2","pages":"261-276"},"PeriodicalIF":2.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired glucose tolerance and insulin resistance in a prenatally-androgenized rat model of polycystic ovary syndrome in later life.","authors":"Mahbanoo Farhadi-Azar, Mahsa Noroozzadeh, Maryam Mousavi, Marzieh Saei Ghare Naz, Fahimeh Ramezani Tehrani","doi":"10.1113/EP091912","DOIUrl":"https://doi.org/10.1113/EP091912","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive-aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally-androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3-20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754831","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}

{"title":"Iliac branch endoprosthesis for endovascular treatment of complex aorto-iliac aneurysms - from device design to practical experience: how to translate physiology considerations into clinical applications.","authors":"Apostolos G Pitoulias, Mario D Oria, Konstantinos P Donas, Matti Jubouri, Damian M Bailey, Ian M Williams, Mohamad Bashir","doi":"10.1113/EP091801","DOIUrl":"https://doi.org/10.1113/EP091801","url":null,"abstract":"<p><p>This article provides a narrative review of the current literature and our expert opinion concerning the iliac branch endoprosthesis (IBE) and its use in the treatment of complex abdominal aortic aneurysm (AAA) cases with concomitant aneurysmal involvement of the common iliac artery (CIA) and/or the internal iliac artery (IIA). Up to 25% of those with an AAA may present with extension of the aneurysmal disease into the iliac vessels. This anatomy may complicate the standard endovascular aortic repair (EVAR) procedure, as the available length of distal landing zones is altered. The optimum treatment requires both the adequate sealing of the distal landing zone as well as the preservation of the pelvic circulation through the IIA. Extensive preoperative assessment of the anatomy, as well as an accurate deployment following all procedural steps, enables endovascular treatment of complex aorto-iliac aneurysms safe with excellent midterm clinical outcomes. The current literature shows that the utilization of the IBE offers a durable treatment of these complicated cases with results equal to those of the open repair, without the associated morbidity. Preservation of the pelvic circulation is recommended to prevent pelvic ischaemic symptoms and can also be carried out on both sides provided certain anatomical requirements are met.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754827","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}

{"title":"My journey from an early researcher to an aspiring medic: A dance from bench to bedside.","authors":"Jaspreet Kaur","doi":"10.1113/EP092239","DOIUrl":"https://doi.org/10.1113/EP092239","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727343","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}

{"title":"Brown and beige adipose tissue-derived metabokine and lipokine inter-organ signalling in health and disease.","authors":"Anna Malicka, Aysha Ali, Amanda D V MacCannell, Lee D Roberts","doi":"10.1113/EP092008","DOIUrl":"https://doi.org/10.1113/EP092008","url":null,"abstract":"<p><p>Adipose tissue has an established endocrine function through the secretion of adipokines. However, a role for bioactive metabolites and lipids, termed metabokines and lipokines, is emerging in adipose tissue-mediated autocrine, paracrine and endocrine signalling and inter-organ communication. Traditionally seen as passive entities, metabolites are now recognized for their active roles in regulating cellular signalling and local and systemic metabolism. Distinct from white adipose tissue, specific endocrine functions have been attributed to thermogenic brown and beige adipose tissues. Brown and beige adipose tissues have been identified as sources of metabokines and lipokines, which influence diverse metabolic pathways, such as fatty acid β-oxidation, mitochondrial function and glucose homeostasis, across a range of tissues, including skeletal muscle, adipose tissue and heart. This review explores the intricate signalling mechanisms of brown and beige adipose tissue-derived metabokines and lipokines, emphasizing their roles in maintaining metabolic homeostasis and their potential dysregulation in metabolic diseases. Furthermore, we discuss the therapeutic potential of targeting these pathways, proposing that precise modulation of metabokine receptors and transporters could offer superior specificity and efficacy in comparison to conventional approaches, such as β-adrenergic signalling-stimulated activation of brown adipose tissue thermogenesis. Understanding the complex interactions between adipokines, metabokines and lipokines is essential for developing a systems-level approach to new interventions for metabolic disorders, underscoring the need for continued research in this rapidly evolving field.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727339","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}

{"title":"Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex","authors":"Yelena Bibineyshvili,&nbsp;Thomas J. Vajtay,&nbsp;Shiva Salsabilian,&nbsp;Nicholas Fliss,&nbsp;Aastha Suvarnakar,&nbsp;Jennifer Fang,&nbsp;Shavonne Teng,&nbsp;Janet Alder,&nbsp;Laleh Najafizadeh,&nbsp;David J. Margolis","doi":"10.1113/EP092219","DOIUrl":"10.1113/EP092219","url":null,"abstract":"<p>Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 2","pages":"321-344"},"PeriodicalIF":2.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring position sense.","authors":"Uwe Proske","doi":"10.1113/EP092190","DOIUrl":"https://doi.org/10.1113/EP092190","url":null,"abstract":"<p><p>Position sense is arguably more important than any of the other proprioceptive senses, because it provides us with information about the position of our body and limbs in relationship to one another and to our surroundings; it has been considered to contribute to our self-awareness. There is currently no consensus over the best method of measuring position sense. We have recently measured position sense with three commonly used methods. These were two-arm matching, one-arm pointing and one-arm repositioning, all carried out by blindfolded subjects with their lightly loaded forearms moving in the sagittal plane. It is currently believed that muscle spindles are the principal position sensors. We posed the question, was there evidence for spindles participating in the generation of position sense with each method? The indicator of spindle activity we used was the presence of thixotropic errors in the position signal, in response to conditioning voluntary contractions of forearm muscles. Based on this criterion, there was evidence of spindles contributing to position sense with all three methods. It was concluded that the spindle contribution to the position signal and the extent to which this was processed centrally was different with each method. It is argued that a case could be made for the existence of more than one position sense. Differences between the methods have implications for their meaning in a clinical setting.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686590","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}

{"title":"Inhibition of TrkB kinase activity impairs autophagy in cervical motor neurons of young but not old mice","authors":"Miguel Pareja-Cajiao,&nbsp;Heather M. Gransee,&nbsp;Sepideh Jahanian,&nbsp;Gary C. Sieck,&nbsp;Carlos B. Mantilla","doi":"10.1113/EP092095","DOIUrl":"10.1113/EP092095","url":null,"abstract":"<p>Ageing-related neuromuscular dysfunction is associated with reduced tropomyosin-related kinase receptor subtype B (TrkB) signalling and accumulation of damaged cytoplasmic aggregates in motor neurons. Autophagy functions to remove these damaged aggregates, and we previously reported increased cervical motor neuron expression of LC3 and p62 in old age. We hypothesized that inhibition of TrkB kinase activity results in an increase in the relative expression of both LC3 and p62 in cervical motor neurons, consistent with impaired progression of autophagy. <i>TrkB^F616A</i> mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were treated at 6, 18 or 24 months of age with vehicle or 1NMPP1 for 7 days. Immunofluorescence intensity was measured to determine LC3 and p62 expression in choline acetyltransferase-positive motor neurons in the cervical spinal cord. The effect of inhibiting TrkB kinase activity on progression of autophagy was age dependent. In 6-month-old mice, inhibiting TrkB kinase activity increased cervical motor neuron expression of LC3 by 11% (<i>P</i> &lt; 0.001) and p62 by 8% (<i>P</i> = 0.019) compared with vehicle treatment. In 18- and 24-month-old mice, there was no effect of inhibiting TrkB kinase activity on motor neuron LC3 or p62 expression. We provide evidence that inhibition of TrkB signalling impairs progression of autophagy in motor neurons of young mice, similar to the response to ageing. Accordingly, a reduction of TrkB signalling in old age might contribute to neuromuscular dysfunction by impairing progression of autophagy in motor neurons.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 1","pages":"166-178"},"PeriodicalIF":2.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11689133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Born high, born fast: Does highland birth confer a pulmonary advantage for sea level endurance?","authors":"Hunter L Paris, Marissa N Baranauskas, Keren Constantini, Ren-Jay Shei, Peyton E Allen, John R Jadovitz, Chad C Wiggins, Cooker Perkins Storm","doi":"10.1113/EP091830","DOIUrl":"https://doi.org/10.1113/EP091830","url":null,"abstract":"<p><p>Less than 7% of the world's population live at an altitude above 1500 m. Yet, as many as 67% of medalists in the 2020 men's and women's Olympic marathon, and 100% of medalists in the 2020 men's and women's Olympic 5000 m track race may have been born or raised above this otherwise rare threshold. As a possible explanation, research spanning nearly a quarter of a century demonstrates that indigenous highlanders exhibit pulmonary adaptations distinct from their lowland counterparts. These adaptations may then promote endurance performance. Indeed, healthy indigenous highlanders often exhibit a larger aerobic exercise capacity compared to sea-level residents who travel to high altitude. However, questions remain on whether high-altitude birth is advantageous for sea-level competitions. In this review, we ask whether being born at a high altitude generates an ergogenic advantage for endurance performance in the Summer Olympics-a venue that is generally held at sea level. In so doing, we distinguish between three groups of high-altitude residents: (i) the indigenous highlander, (ii) the highland newcomer, and (iii) the highland sojourner. Concentrating specifically on altitude-induced alterations to pulmonary physiology beginning in the perinatal period, we propose that if altitude-related maladaptations are avoided, genomic and developmental alterations accompanying highland birth may present benefits for endurance competitions at sea level.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692832","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}

{"title":"Aerobic capacity and muscle proteome: Insights from a mouse model","authors":"Abel Plaza-Florido,&nbsp;Alejandro Santos-Lozano,&nbsp;Susana López-Ortiz,&nbsp;Beatriz G. Gálvez,&nbsp;Joaquín Arenas,&nbsp;Miguel A. Martín,&nbsp;Pedro L. Valenzuela,&nbsp;Tomàs Pinós,&nbsp;Alejandro Lucia,&nbsp;Carmen Fiuza-Luces","doi":"10.1113/EP092308","DOIUrl":"10.1113/EP092308","url":null,"abstract":"<p>We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (<i>n</i> = 10) and wild-type (<i>n</i> = 8) mice, as models of intrinsically ‘low’ and ‘normal’ AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromatography with tandem mass spectrometry, with the Search Tool for the Retrieval of Interacting Genes/Proteins database used to generate protein–protein interaction (PPI) networks and enrichment analyses. AC was significantly associated (<i>P</i>-values ranging from 0.0002 to 0.049) with 73 (McArdle) and 61 (wild-type) proteins (<i>r</i>-values from −0.90 to 0.94). These proteins were connected in PPI networks that enriched biological processes involved in skeletal muscle structure/function in both groups (false discovery rate &lt;0.05). In McArdle mice, the proteins associated with AC were involved in skeletal muscle fibre differentiation/development, lipid oxidation, mitochondrial function and calcium homeostasis, whereas in wild-type animals AC-associated proteins were related to cytoskeleton structure (intermediate filaments), cell cycle regulation and endocytic trafficking. Two proteins (WEE2, THYG) were associated with AC (negatively and positively, respectively) in both groups. Only 14 of the 132 proteins (∼11%) associated with AC in McArdle or wild-type mice were also associated with those previously reported to be modified by aerobic training in these mice, providing preliminary evidence for a large divergence in the muscle proteome signature linked to aerobic training or AC, irrespective of AC (intrinsically low or normal) levels. Our findings might help to gain insight into the molecular mechanisms underlying AC at the muscle tissue level.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 2","pages":"293-306"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}