Pflugers Archiv : European journal of physiology最新文献

{"title":"Estrogen hindrance escalates inflammation and neurodegeneration in the hippocampal regions of collagen-induced arthritis female Sprague-Dawley rats.","authors":"Zuo Hao Lee, Wong Siew Tung, Kabileshvaran A/L Jana Santhiran, Huma Shahzad, Nelli Giribabu, Naguib Salleh","doi":"10.1007/s00424-024-03032-w","DOIUrl":"https://doi.org/10.1007/s00424-024-03032-w","url":null,"abstract":"<p><p>This study aims to investigate the effect of estrogen hindrance, i.e., menopause in women for instance with rheumatoid arthritis on the brain hippocampal region by using collagen-induced arthritis (CIA) female rat model (RA). CIA was induced in female rats by injecting bovine type II collagen and incomplete Freund's adjuvant. Estrogen receptor antagonist, fulvestrant (Ful), was given to RA rats to create estrogen hindrance. Control (C) and RA rats were injected with saline and DMSO, respectively, while RA + Ful rats received a 7-day fulvestrant injection. Following experiment completion, rats were sacrificed, and brains were harvested. Brains were stained with H&E and cresyl violet staining and morphological changes in the hippocampus were identified. Additionally, oxidative stress, inflammatory, and apoptosis markers' levels in the hippocampus were analyzed by qPCR, ELISA, and immunohistochemistry techniques. RA + Ful rats showed neuronal atrophy and reduced neurogenesis in the hippocampal regions. NOX4, NF-κB, IL-1β, IL-6, TNF-α, IKK-β, and Bax protein expression levels in the hippocampus were increased, whereas hippocampal Bcl-2, caspase-3, caspase-9, and IGF-1R protein expression levels were decreased. Furthermore, RA + Ful rats had lower levels of antioxidants PON-1 and catalase in the hippocampal regions. The changes in these molecular markers were statistically significant when compared to RA rats without Ful treatment (p < 0.05). Estrogen hindrance exaggerated oxidative stress, inflammation, and apoptosis which resulted in neuronal degeneration in the hippocampal regions in rheumatoid arthritis.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682405","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 lateral habenula regulates stress-related respiratory responses via the monoaminergic system.","authors":"Riko Mizukami, Masayuki Matsumoto, Tadachika Koganezawa","doi":"10.1007/s00424-024-03043-7","DOIUrl":"10.1007/s00424-024-03043-7","url":null,"abstract":"<p><p>Psychologic stress induces behavioral and autonomic responses such as acceleration of respiration. The lateral habenula (LHb) is noted to be involved in stress-induced behavioral responses. However, its involvement in stress-induced respiratory responses is unknown. In this study, we aimed to analyze whether and how the LHb regulates respiration. Electrical stimulation of the LHb of anesthetized Wistar male rats increased respiratory frequency and minute ventilation, calculated by respiratory frequency × thoracic movement amplitude. Systemic administration of a dopaminergic receptor antagonist, clozapine, suppressed the LHb-induced respiratory responses. On the other hand, administration of a serotonergic receptor antagonist, methysergide, significantly accelerated the LHb-induced increase in respiratory frequency, together with suppressing the thoracic movement amplitude. To clarify the source of dopaminergic modulation, we inhibited the ventral tegmental area (VTA), which contains dopaminergic neurons and receives inputs from the LHb, by administering microinjections of a GABA_A agonist, muscimol. The bilateral inhibition of the VTA almost abolished the LHb-induced respiratory responses. These results suggest that LHb activation causes respiration acceleration, mainly mediated by dopaminergic neurons in the VTA and suppressively modulated by the serotonergic system. Neural circuits originating in the LHb may be a key modulator for respiration during psychological stress.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668573","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":"Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.","authors":"Angela Di Porzio, Valentina Barrella, Luisa Cigliano, Gianluigi Mauriello, Antonio Dario Troise, Andrea Scaloni, Susanna Iossa, Arianna Mazzoli","doi":"10.1007/s00424-024-03041-9","DOIUrl":"https://doi.org/10.1007/s00424-024-03041-9","url":null,"abstract":"<p><p>Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625942","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":"Fatiguing high-intensity intermittent exercise depresses maximal Na⁺-K⁺-ATPase activity in human skeletal muscle assessed using a novel NADH-coupled assay.","authors":"Jeppe F Vigh-Larsen, Sara M Frangos, Kristian Overgaard, Graham P Holloway, Magni Mohr","doi":"10.1007/s00424-024-03036-6","DOIUrl":"https://doi.org/10.1007/s00424-024-03036-6","url":null,"abstract":"<p><p>The Na⁺-K⁺-ATPase is a critical regulator of ion homeostasis during contraction, buffering interstitial K⁺ accumulation, which is linked to muscle fatigue during intense exercise. Within this context, we adopted a recently reported methodology to examine exercise-induced alterations in maximal Na⁺-K⁺-ATPase activity. Eighteen trained healthy young males completed a repeated high-intensity cycling protocol consisting of three periods (EX1-EX3) of intermittent exercise. Each period comprised 10 × 45-s cycling at ~ 105% W_max and a repeated sprint test. Muscle biopsies were sampled at baseline and after EX3 for determination of maximal in vitro Na⁺-K⁺-ATPase activity. Blood was drawn after each period and in association with a 2-min cycling test at a standardized high intensity (~ 90% W_max) performed before and after the session to assess plasma K⁺ accumulation. Further, a 5-h recovery period with the ingestion of carbohydrate or placebo supplementation was implemented to explore potential effects of carbohydrate availability before sampling a final biopsy and repeating all tests. A ~ 12% reduction in maximal Na⁺-K⁺-ATPase activity was demonstrated following EX3 compared to baseline (25.2 ± 3.9 vs. 22.4 ± 4.8 μmol·min^-1·g^-1 protein, P = 0.039), which was sustained at the recovery time point (~ 15% decrease compared to baseline to 21.6 ± 5.9 μmol·min^-1·g^-1 protein, P = 0.008). No significant effect of carbohydrate supplementation was observed on maximal Na⁺-K⁺-ATPase activity after recovery (P = 0.078). In conclusion, we demonstrate an exercise-induced depression of maximal Na⁺-K⁺-ATPase activity following high-intensity intermittent exercise, which was sustained during a 5-h recovery period and unrelated to carbohydrate availability under the present experimental conditions. This was shown using a novel NADH coupled assay and confirms previous findings using other methodological approaches.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623480","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 cAMP signaling-induced Ca²⁺ influx mediated by calcium homeostasis modulator 1 (CALHM1) in human odontoblasts.","authors":"Maki Kimura, Sachie Nomura, Takehito Ouchi, Ryuya Kurashima, Rei Nakano, Hinako Sekiya, Hidetaka Kuroda, Kyosuke Kono, Yoshiyuki Shibukawa","doi":"10.1007/s00424-024-03038-4","DOIUrl":"https://doi.org/10.1007/s00424-024-03038-4","url":null,"abstract":"<p><p>In odontoblasts, intracellular Ca²⁺ signaling plays key roles in reactionary dentin formation and generation of dentinal pain. Odontoblasts also express several G_s protein-coupled receptors that promote production of cyclic AMP (cAMP). However, the crosstalk between intracellular cAMP and Ca²⁺ signaling, as well as the role of cAMP in the cellular functions of odontoblasts, remains unclear. In this study, we measured intracellular cAMP levels and intracellular free Ca²⁺ concentration ([Ca²⁺]_i). We also investigated the effect of intracellular cAMP on mineralization by the odontoblasts. In the presence of extracellular Ca²⁺, the application of forskolin (adenylyl cyclase activator) or isoproterenol (G_s protein-coupled beta-2 adrenergic receptor agonist) increased intracellular cAMP levels and [Ca²⁺]_i in odontoblasts. The [Ca²⁺]_i increases could not be observed by removing extracellular Ca²⁺, indicating that cAMP is capable to activate Ca²⁺ entry. Forskolin-induced [Ca²⁺]_i increase was inhibited by a protein kinase A inhibitor in odontoblasts. The [Ca²⁺]_i increase was sensitive to Gd³⁺, 2APB, or Zn²⁺ but not verapamil, ML218, or La³⁺. In immunofluorescence analyses, odontoblasts were immunopositive for calcium homeostasis modulator 1 (CALHM1), which was found close to ionotropic ATP receptor subtype, P2X₃ receptors. When CALHM1 was knocked down, forskolin-induced [Ca²⁺]_i increase was suppressed. Alizarin red and von Kossa staining showed that forskolin decreased mineralization. These findings suggest that activation of adenylyl cyclase elicited increases in the intracellular cAMP level and Ca²⁺ influx via protein kinase A activation in odontoblasts. Subsequent cAMP-dependent Ca²⁺ influx was mediated by CALHM1 in odontoblasts. In addition, the intracellular cAMP signaling pathway in odontoblasts negatively mediated dentinogenesis.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623485","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":"Obituary for Prof. Stephen (Ben) Walsh, Professor of Nephrology at University College London.","authors":"Andrew M Hall, Robert J Unwin, Matthew Bailey, Chris Laing","doi":"10.1007/s00424-024-03042-8","DOIUrl":"https://doi.org/10.1007/s00424-024-03042-8","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583991","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 emerging roles of necroptosis in skeletal muscle health and disease.","authors":"Rizwan Qaisar","doi":"10.1007/s00424-024-02994-1","DOIUrl":"10.1007/s00424-024-02994-1","url":null,"abstract":"<p><p>Necroptosis is a regulated form of cell death with implications in various physiological and pathological processes in multiple tissues. However, the relevant findings from post-mitotic tissues, such as skeletal muscle, are scarce. This review summarizes the potential contributions of necroptosis to skeletal muscle health and diseases. It first discusses the physiological roles of necroptosis in muscle regeneration and development. It then summarizes the contributions of necroptosis to the pathogenesis of multiple muscle diseases, including muscular dystrophies, inflammatory myopathies, cachexia, and neuromuscular disorders. Lastly, it unravels the gaps in our understanding and therapeutic challenges of inhibiting necroptosis as a potential intervention for muscle diseases. Specifically, the findings from the transgenic animal models and the use of pharmacological inhibitors of necroptosis are discussed with relevance to improving the structure and/or function of skeletal muscle in various diseases. Recent developments from experimental animal models and clinical data are presented to discuss the roles of necroptosis in skeletal muscle health and diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1645-1651"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734861","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":"Enhancement of physiology via adaptive transcription.","authors":"Thomas Lissek","doi":"10.1007/s00424-024-03037-5","DOIUrl":"https://doi.org/10.1007/s00424-024-03037-5","url":null,"abstract":"<p><p>The enhancement of complex physiological functions such as cognition and exercise performance in healthy individuals represents a challenging goal. Adaptive transcription programs that are naturally activated in animals to mediate cellular plasticity in response to stimulation can be leveraged to enhance physiological function above wild-type levels in young organisms and counteract complex functional decline in aging. In processes such as learning and memory and exercise-dependent muscle remodeling, a relatively small number of molecules such as certain stimulus-responsive transcription factors and immediate early genes coordinate widespread changes in cellular physiology. Adaptive transcription can be targeted by various methods including pharmaceutical compounds and gene transfer technologies. Important problems for leveraging adaptive transcription programs for physiological enhancement include a better understanding of their dynamical organization, more precise methods to influence the underlying molecular components, and the integration of adaptive transcription into multi-scale physiological enhancement concepts.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558463","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 role of non-coding RNAs in neuropathic pain.","authors":"Xiuying He, Huisi Yang, Yuexiang Zheng, Xiaoming Zhao, Tinghua Wang","doi":"10.1007/s00424-024-02989-y","DOIUrl":"10.1007/s00424-024-02989-y","url":null,"abstract":"<p><p>Neuropathic pain (NPP) is a refractory pain syndrome, caused by damage or disease of the somatosensory nervous system and characterized by spontaneous pain, hyperalgesia, abnormal pain and sensory abnormality. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and Piwi interacting RNA (piRNA), play a notable role in initiation and maintenance of NPP. In this review, we summarize the role of ncRNAs in NPP and their underlaying mechanism. Generally, ncRNAs are interacted with mRNA, protein or DNA to regulate the molecules and signals assciated with neuroinflammation, ion channels, neurotrophic factors and others, and then involved in the occurrence and development of NPP. Therefore, this review not only contributes to deepen our understanding of the pathophysiological mechanism of NPP, but also provides theoretical basis for the development of new therapy strategies for this disorder.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1625-1643"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627341","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":"BK channels promote action potential repolarization in skeletal muscle but contribute little to myotonia.","authors":"Chris Dupont, Brianna Blake, Andrew A Voss, Mark M Rich","doi":"10.1007/s00424-024-03005-z","DOIUrl":"10.1007/s00424-024-03005-z","url":null,"abstract":"<p><p>Patients with myotonia congenita suffer from slowed relaxation of muscle (myotonia), due to hyperexcitability caused by loss-of-function mutations in the ClC-1 chloride channel. A recent study suggested that block of large-conductance voltage- and Ca²⁺- activated K⁺ channels (BK) may be effective as therapy. The mechanism underlying efficacy was suggested to be lessening of the depolarizing effect of build-up of K⁺ in t-tubules of muscle during repetitive firing. BK channels are widely expressed in the nervous system and have been shown to play a central role in regulation of excitability, but their contribution to muscle excitability has not been determined. We performed intracellular recordings as well as force measurements in both wild type and BK^-/- mouse extensor digitorum longus muscles. Action potential width was increased in BK^-/- muscle due to slowing of repolarization, consistent with the possibility K⁺ build-up in t-tubules is lessened by block of BK channels in myotonic muscle. However, there was no difference in the severity of myotonia triggered by block of muscle Cl^- channels with 9-anthracenecarboxylic acid (9AC) in wild type and BK^-/- muscle fibers. Further study revealed no difference in the interspike membrane potential during repetitive firing suggesting there was no reduction in K⁺ build-up in t-tubules of BK^-/- muscle. Force recordings following block of muscle Cl^- channels demonstrated little reduction in myotonia in BK^-/- muscle. In contrast, the current standard of care, mexiletine, significantly reduced myotonia. Our data suggest BK channels regulate muscle excitability, but are not an attractive target for therapy of myotonia.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1693-1702"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988527","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}