Pflugers Archiv : European journal of physiology最新文献

{"title":"Microbiota, mitochondria, and epigenetics in health and disease: converging pathways to solve the puzzle.","authors":"Natalia Lucia Rukavina Mikusic, Paula Denise Prince, Marcelo Roberto Choi, Luiz Gustavo A Chuffa, Vinícius Augusto Simão, Claudia Castro, Walter Manucha, Isabel Quesada","doi":"10.1007/s00424-025-03072-w","DOIUrl":"10.1007/s00424-025-03072-w","url":null,"abstract":"<p><p>Dysbiosis, which refers to an imbalance in the composition of the gut microbiome, has been associated with a range of metabolic disorders, including type 2 diabetes, obesity, and metabolic syndrome. Although the exact mechanisms connecting gut dysbiosis to these conditions are not fully understood, various lines of evidence strongly suggest a substantial role for the interaction between the gut microbiome, mitochondria, and epigenetics. Current studies suggest that the gut microbiome has the potential to affect mitochondrial function and biogenesis through the production of metabolites. A well-balanced microbiota plays a pivotal role in supporting normal mitochondrial and cellular functions by providing metabolites that are essential for mitochondrial bioenergetics and signaling pathways. Conversely, in the context of illnesses, an unbalanced microbiota can impact mitochondrial function, leading to increased aerobic glycolysis, reduced oxidative phosphorylation and fatty acid oxidation, alterations in mitochondrial membrane permeability, and heightened resistance to cellular apoptosis. Mitochondrial activity can also influence the composition and function of the gut microbiota. Because of the intricate interplay between nuclear and mitochondrial communication, the nuclear epigenome can regulate mitochondrial function, and conversely, mitochondria can produce metabolic signals that initiate epigenetic changes within the nucleus. Given the epigenetic modifications triggered by metabolic signals from mitochondria in response to stress or damage, targeting an imbalanced microbiota through interventions could offer a promising strategy to alleviate the epigenetic alterations arising from disrupted mitochondrial signaling.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"635-655"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670557","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":"The NFAT5 chronicles: a transcription factor's tale of hypoxia, pulmonary drama, and endothelial resilience to hypoxia.","authors":"Dörthe M Katschinski","doi":"10.1007/s00424-025-03080-w","DOIUrl":"10.1007/s00424-025-03080-w","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"683-684"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736122","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":"Spatio-temporal segregation between sensory relay and swallowing pre-motor population activities by optical imaging in the rat nucleus of the solitary tract.","authors":"Shinya Fuse, Yoichiro Sugiyama, Rishi R Dhingra, Shigeru Hirano, Mathias Dutschmann, Yasumasa Okada, Yoshitaka Oku","doi":"10.1007/s00424-025-03065-9","DOIUrl":"10.1007/s00424-025-03065-9","url":null,"abstract":"<p><p>The nucleus tractus solitarius (NTS) contains neurons that relay sensory swallowing commands information from the oropharyngeal cavity and swallowing premotor neurons of the dorsal swallowing group (DSG). However, the spatio-temporal dynamics of the interplay between the sensory relay and the DSG is not well understood. Here, we employed fluorescence imaging after microinjection of the calcium indicator into the NTS in an arterially perfused brainstem preparation of rat (n = 8) to investigate neuronal population activity in the NTS in response to superior laryngeal nerve (SLN) stimulation. Respiratory and swallowing motor activities were determined by simultaneous recordings of phrenic and vagal nerve activity (PNA, VNA). The analysis of SLN stimulation near the threshold triggering a swallowing allowed us to analyze Ca²⁺ signals related to the sensory relay and the DSG. We show that activation of sensory relay neurons triggers spatially confined Ca²⁺ signals exclusively unilateral to the stimulated SLN at short latencies (114.3 ± 94.4 ms). However, SLN-evoked swallowing triggered Ca²⁺ signals bilaterally at longer latencies (200 ± 145.2 ms) and engaged anatomically distributed DSG activity across the dorsal medulla oblongata. The Ca²⁺ signals originating from the DSG preceded evoked VNA swallow motor bursts, thus the swallowing premotor neurons that drive laryngeal motor pools are located outside the DSG. In conclusion, the study illuminates the spatial-temporal features of sensory-motor integration of swallowing in the NTS and further supports the hypothesis that the NTS harbors swallowing pre-motor neurons that may generate the swallowing motor activity, while first-order pre-motor pools are located outside the DSG.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"719-727"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040911","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":"Epidemiology of metabolic syndrome.","authors":"Iris Pigeot, Wolfgang Ahrens","doi":"10.1007/s00424-024-03051-7","DOIUrl":"10.1007/s00424-024-03051-7","url":null,"abstract":"<p><p>The global increase of overweight and obesity in children and adults is one of the most prominent public health threats, often accompanied by insulin resistance, hypertension, and dyslipidemia. The simultaneous occurrence of these health problems is referred to as metabolic syndrome. Various criteria have been proposed to define this syndrome, but no general consensus on the specific markers and the respective cut-offs has been achieved yet. As a consequence, it is difficult to assess regional variations and temporal trends and to obtain a comprehensive picture of the global burden of this major health threat. This limitation is most striking in childhood and adolescence, when metabolic parameters change with developmental stage. Obesity and related metabolic disorders develop early in life and then track into adulthood, i.e., the metabolic syndrome seems to originate in the early life course. Thus, it would be important to monitor the trajectories of cardio-metabolic parameters from early on. We will summarize selected key studies to provide a narrative overview of the global epidemiology of the metabolic syndrome while considering the limitations that hinder us to provide a comprehensive full picture of the problem. A particular focus will be given to the situation in children and adolescents and the risk factors impacting on their cardio-metabolic health. This summary will be complemented by key findings of a pan-European children cohort and first results of a large German adult cohort.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"669-680"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040888","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":"The enigma of ENaC activation by proteolytic cleavage: a never ending quest?","authors":"Eric Feraille, Ali Sassi, Monika Gjorgjieva","doi":"10.1007/s00424-025-03081-9","DOIUrl":"10.1007/s00424-025-03081-9","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"681-682"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753408","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":"The obesity pandemic and its impact on non-communicable disease burden.","authors":"Staffan Hildebrand, Alexander Pfeifer","doi":"10.1007/s00424-025-03066-8","DOIUrl":"10.1007/s00424-025-03066-8","url":null,"abstract":"<p><p>The rising prevalence of overweight and obesity across the globe is a major threat both to public health and economic development. This is mainly due to the link of obesity with the development and outcomes of non-communicable diseases (NCDs). NCDs are a leading cause of global death and disability, and reducing the burden of NCDs on patients and healthcare systems is of critical importance to improve public health. Obesity is projected to be the number one preventable risk factor for NCDs by 2035, and there is an urgent need to tackle the growing obesity rates in order to reduce NCD incidence and severity. Here, we review the current understanding of the impact of obesity on NCD burden in general, as well as the epidemiological and mechanistic relationship between obesity and some of the most common classes of NCDs. By literature review, we found that over 70% of NCDs have a documented association with obesity, highlighting the importance of a better understanding of the pathophysiologies underlying obesity/overweight as well as the interaction between obesity and NCDs in order to reduce global disease burden.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"657-668"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383018","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":"Intrinsic responses to hypoxia and hypercapnia of neurons in the cardiorespiratory center of the ventral medulla of newborn rats.","authors":"Hiroshi Onimaru, Yui Koyanagi, Kamon Iigaya, Keiko Ikeda, Masahiko Izumizaki","doi":"10.1007/s00424-025-03077-5","DOIUrl":"10.1007/s00424-025-03077-5","url":null,"abstract":"<p><p>The rostral ventrolateral medulla (RVLM) includes a variety of neurons essential for cardiorespiratory control. Although some of these neurons are thought to be intrinsically sensitive to hypercapnia and/or hypoxia, relationships between types of neurons and responses to hypoxia and/or hypercapnia are not well understood. Tyrosine hydroxylase (TH) is one of the cell-type markers of the RVLM neurons. Here, we report effects of hypoxia and hypercapnia on TH-positive or -negative neurons in the RVLM of newborn rats. Brainstem-spinal cord preparations were isolated from 0-3-day-old Wistar rats and superfused with artificial cerebrospinal fluid equilibrated with 95% O₂ and 5% CO₂, pH 7.4 at 25-26 °C. Membrane potential responses to hypoxia (95% → 0% O₂) and/or hypercapnia (2% → 8% CO₂) were examined in the presence of tetrodotoxin (TTX) after identification of the firing pattern. We found that TH-positive C1 neurons in the RVLM were sensitive to hypoxia with membrane depolarization but less sensitive to hypercapnia. TH-negative neurons in the C1 area showed responses similar to those of C1 neurons. Moreover, C1 area neurons remained depolarized by hypoxia in the presence of TTX plus gliotransmitter blockers. In contrast, Phox2b-positive and TH-negative neurons in the parafacial respiratory group were intrinsically sensitive to CO₂ but not sensitive to hypoxia. Respiratory-related neurons (Phox2b and TH negative) showed a variable response to hypoxia: unchanging, depolarizing, or hyperpolarizing. Our findings suggest that C1 area neurons in the RVLM are intrinsically sensitive to hypoxia and belong to one of the elements constituting central hypoxic sensors.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"685-705"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693043","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":"Neuronal subtype-dependent kinetics of EPSCs induced by thalamocortical projections from the ventroposteromedial thalamic nucleus to the insular cortex in rats.","authors":"Yuko Koyanagi, Kiyofumi Yamamoto, Kouhei Kitano, Mie Kajiwara, Masayuki Kobayashi","doi":"10.1007/s00424-025-03074-8","DOIUrl":"10.1007/s00424-025-03074-8","url":null,"abstract":"<p><p>Cerebrocortical neurons receive glutamatergic inputs via thalamocortical projections, and their activities are simultaneously controlled by GABAergic interneurons. Few studies have demonstrated the difference in the amplitude of evoked excitatory postsynaptic currents (EPSCs) via thalamocortical projections onto glutamatergic excitatory (ENs) and GABAergic inhibitory neurons (INs); the strength of excitation among neural subtypes varies among sensory cortices. The present study aimed to reveal the profile of thalamocortical inputs to ENs and inhibitory neurons in the insular cortex (IC) by evaluating the amplitude and latency of EPSCs evoked in the connection from the ventroposteromedial (VPM) thalamic nucleus to the IC. Whole-cell patch-clamp recordings were prepared from ENs, fast-spiking neurons (FSNs), and non-fast-spiking neurons (NFSNs) in the middle layers (layer 4 and adjacent layers) of the IC. Photostimulation-induced EPSCs (pEPSCs) were evoked via the selective activation of thalamocortical axons via optogenetics. All the neuronal subtypes received direct excitatory inputs from the VPM, and pEPSCs recorded from FSNs had the greatest amplitude and shortest latency compared with those recorded from ENs and NFSNs. Under current-clamp conditions, FSNs almost invariably exhibited action potentials responding to photostimulation, whereas ENs and NFSNs often showed the failure of action potential induction. In addition to excitatory inputs, some neurons exhibited pEPSCs followed by outward GABA_A receptor-mediated currents, which curtailed the pEPSC peak and aligned the timing of the action potential to photostimulation. These results suggested that FSNs play a role in the feedforward inhibition of EN activity in the upper layer of the IC. (244 words).</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"707-717"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630869","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":"Intracellular pH regulates the strength of the intrinsic inward rectification of Kir4.1/Kir5.1 channels.","authors":"Iván A Aréchiga-Figueroa, Leticia G Marmolejo-Murillo, Mayra Delgado-Ramírez, Rodrigo Zamora-Cárdenas, Eloy G Moreno-Galindo, Tania Ferrer, Ricardo A Navarro-Polanco, José A Sánchez-Chapula, Aldo A Rodríguez-Menchaca","doi":"10.1007/s00424-025-03079-3","DOIUrl":"10.1007/s00424-025-03079-3","url":null,"abstract":"<p><p>Kir4.1/Kir5.1 channels play a crucial role in important physiological functions, notably in the kidneys and brain. A hallmark of these channels is the coexistence of two mechanisms of inward rectification: the classical \"extrinsic\" inward rectification induced by polyamines and Mg²⁺ blocking the pore, and a novel \"intrinsic\" voltage-dependent mechanism driven by K⁺ flux. Previous studies have shown that Kir4.1/Kir5.1 channels are modulated by the intracellular pH in the physiological range. Here, we investigated the influence of the intracellular pH on the extent of the intrinsic inward rectification of Kir4.1/Kir5.1 channels expressed in HEK-293 cells and recorded using the inside-out configuration of the patch-clamp technique. We found that mutations that are known to modulate the pH sensitivity of Kir4.1/Kir5.1 channels attenuated inward rectification. The combination of these mutations in the triple mutant channel Kir4.1(K67M)/Kir5.1(N161E-R230E) virtually abolished inward rectification at pH 7.4; however, this property was re-established at acidic pH values. Consistently, the strong inward rectification of wild-type Kir4.1/Kir5.1 channels was reduced by intracellular alkalinization and further enhanced by acidification. Altogether, these experiments indicate that the intracellular pH strongly regulates the strength of the intrinsic inward rectification. Furthermore, triple mutant channels retained the extrinsic mechanism of inward rectification at pH 7.4, as can be blocked by spermine, but lost the ability to respond to elevated levels of PIP_2, unlike wild-type channels. Interestingly, whole-cell recordings of wild-type and triple mutant channels imply that the mechanism of intrinsic inward rectification is an important contributor to the overall rectification of Kir4.1/Kir5.1 channels in basal conditions.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"741-752"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710810","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":"Reproducibility of smooth muscle mechanical properties in consecutive stretch and activation protocols.","authors":"Simon Kiem, Stefan Papenkort, Mischa Borsdorf, Markus Böl, Tobias Siebert","doi":"10.1007/s00424-025-03075-7","DOIUrl":"10.1007/s00424-025-03075-7","url":null,"abstract":"<p><p>Mechanical organ models are crucial for understanding organ function and clinical applications. These models rely on input data regarding smooth muscle properties, typically gathered from experiments involving stimulations at different muscle lengths. However, reproducibility of these experimental results is a major challenge due to rapid changes in active and passive smooth muscle properties during the measurement period. Usually, preconditioning of the tissue is employed to ensure reproducible behavior in subsequent experiments, but this process itself alters the tissue's mechanical properties. To address this issue, three protocols (P1, P2, P3) without preconditioning were developed and compared to preserve the initial mechanical properties of smooth muscle tissue. Each protocol included five repetitive experimental cycles with stimulations at a long muscle length, varying in the number of stimulations at a short muscle length (P1: 0, P2: 1, P3: 2 stimulations). Results showed that P2 and P3 successfully reproduced the initial active force at a long length over five cycles, but failed to maintain the initial passive forces. Conversely, P1 was most effective in maintaining constant passive forces over the cycles. These findings are supported by existing adaptation models. Active force changes are primarily due to the addition or removal of contractile units in the contractile apparatus, while passive force changes mainly result from actin polymerization induced by contractions, leading to cytoskeletal stiffening. This study introduces a new method for obtaining reproducible smooth muscle parameters, offering a foundation for future research to replicate the mechanical properties of smooth muscle tissue without preconditioning.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"729-739"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676925","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}