Dhanusha Sivarajan, Vidya Pothayi, Sebastian Chempakassery Devasia, Binu Ramachandran
{"title":"Impact of dietary composition on behavioural expression and gut microbiome dynamics in zebrafish.","authors":"Dhanusha Sivarajan, Vidya Pothayi, Sebastian Chempakassery Devasia, Binu Ramachandran","doi":"10.1007/s00424-025-03139-8","DOIUrl":"10.1007/s00424-025-03139-8","url":null,"abstract":"<p><p>Diet is a key physiological factor shaping brain function and gut microbiota, which together form the dynamic gut-brain axis. This bidirectional communication system plays a pivotal role in regulating behavioural outcomes. Therefore, it is worth investigating various behavioural aspects and connecting them with gut microbial dynamics shaped by differential dietary composition. Using zebrafish, we examined the effects of monotypic and combined diets of live feed and commercial feed on behavioural outcomes, morphometry, and gut microbiota. After chronic dietary intervention, fish receiving a mixed diet (Artemia, pellet, and spirulina) showed behavioural profile with enhanced exploration, reduced anxiety-like behaviour, and moderate aggression, alongside a balanced gut microbial composition. In contrast, monotypic diets produced distinct effects: Artemia-only fish displayed reduced boldness, heightened anxiety, and pathogenic microbial enrichment, while pellet-only fish showed greater growth but increased aggression. These findings highlight the importance of mixed feeding regimens for maintaining healthy gut-brain-behaviour interactions and support zebrafish as a model for studying diet-microbiota-behaviour relationships.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"13"},"PeriodicalIF":3.2,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805278","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":"When does the \"third fluid space\" open?","authors":"Robert G Hahn","doi":"10.1007/s00424-025-03135-y","DOIUrl":"10.1007/s00424-025-03135-y","url":null,"abstract":"<p><p>Recent kinetic studies show that the interstitial space contains two functional fluid compartments. This study explores the prerequisites for accumulation of infused crystalloid fluid in the remote slow-exchange space (\"third fluid space¨, V<sub>t2</sub>). Volume kinetic analysis based on log likelihood mathematics was applied to retrospective data from 132 intravenous infusions in 85 healthy volunteers who received 0.6-2.5 L of crystalloid fluid over 30 min. Frequent measurements of the blood hemoglobin concentration during and after these infusions, together with the measured urine output, served as calculation inputs. Three substudies were set up to illustrate key issues regarding V<sub>t2</sub> filling. In the first of them, infusions were preceded by blood withdrawal, which is known to decrease the interstitial pressure (P<sub>if</sub>). Blood withdrawal resulted in smaller volumes entering V<sub>t2</sub>, confirming that V<sub>t2</sub> filling is dependent on P<sub>if</sub>. In the second substudy, modeled and measured urine outputs were compared after varying the inclusion of V<sub>t2</sub> in kinetic analyses in which the infused volume was gradually increased. Consideration of V<sub>t2</sub> was deemed appropriate when > 1.2 L of fluid was administered. In the third substudy, assessment of V<sub>t2</sub> filling during 7 time periods just before and after the 30 min infusions confirmed that uptake of fluid to V<sub>t2</sub> was initiated between 30 and 35 min. In conclusion, accumulation of fluid in V<sub>t2</sub> is dependent on P<sub>if</sub> and occurs following infusion of > 1.2 L of crystalloid fluid. Uptake is not gradual but is initiated at a specific point in time.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"12"},"PeriodicalIF":3.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12708698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768756","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":"ER stress inhibitor 4PBA attenuates hindlimb unloading-induced cardiac mitochondrial and metabolic dysfunction.","authors":"Firdos Ahmad, Anupriya Sinha, Asima Karim, Megna Srinivas, Josemin Jose, Dhanendra Tomar, Rizwan Qaisar","doi":"10.1007/s00424-025-03146-9","DOIUrl":"10.1007/s00424-025-03146-9","url":null,"abstract":"<p><p>Prolonged bed rest or microgravity exposure, as experienced during spaceflight, profoundly impacts cardiac health. Yet, the molecular mechanisms driving these detrimental changes remain largely elusive. Hindlimb unloading (HLU), a model of simulated microgravity, induces endoplasmic-reticulum (ER) stress, and its role in maladaptive cardiac remodeling remains unknown. To investigate the impact of HLU, its underlying molecular mechanisms and the therapeutic potential of ER stress suppression, C57BL6 mice were assigned to grounded control (GC) or HLU group. HLU mice received daily vehicle or 4-phenylbutyrate (4-PBA), an ER stress inhibitor, for 21 days. Additionally, HL-1 cardiomyocytes were treated with the ER stress inducer thapsigargin, with or without 4-PBA, to explore the cross-communication between ER stress and mitochondrial and metabolic dysfunction in vitro. Cardiac transcriptomic analysis revealed significant gene dysregulation in HLU compared to GC hearts. In HLU hearts, downregulated genes were mainly enriched for mitochondrial function and metabolic pathways, while upregulated genes were linked to extracellular matrix (ECM) pathways. Conversely, HLU mice treated with 4-PBA showed upregulation of mitochondrial function-related genes and downregulation of ECM-related genes. The oxidative phosphorylation (OXPHOS), which was downregulated in HLU hearts, became one of the most upregulated pathways following 4-PBA treatment. Consistent with the in vivo findings, thapsigargin-induced ER stress significantly compromised mitochondrial function, whereas co-treatment with 4PBA significantly preserved mitochondrial function. Together, our findings strongly suggest that prolonged bed rest or microgravity exposure triggers ER stress-induced mitochondrial and metabolic dysfunction in the heart, and pharmacological suppression of ER stress limits these detrimental cellular effects.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"11"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763594","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":"Macrophages in metaflammation - fueling chronic inflammation in metabolic disease.","authors":"Ronja Kardinal, Dagmar Wachten","doi":"10.1007/s00424-025-03141-0","DOIUrl":"10.1007/s00424-025-03141-0","url":null,"abstract":"<p><p>Obesity is a leading global health issue, closely associated with a chronic low-grade inflammation termed metaflammation. Metaflammation is driven by immune cell reprogramming, particularly of macrophages. In white adipose tissue (WAT), obesity induces a shift from anti-inflammatory to pro-inflammatory macrophage phenotypes, contributing to insulin resistance and tissue fibrosis. Recent studies have also illuminated the role of macrophages in brown and beige adipose tissue (BAT and scWAT), where they influence thermogenic capacity. Beyond the adipose tissue, the liver is the other main metabolic organ impacted by obesity. Liver macrophages play a critical role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting inflammation, lipid accumulation, and fibrosis. This review highlights the role of macrophages in the development and regulation of metaflammation in metabolic organs.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"10"},"PeriodicalIF":3.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757223","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":"Mechanism of FOXC1 in the invasion and migration of ectopic endometrial stromal cells in endometriosis.","authors":"Rui Huang, Yan Li, Yun Zhang","doi":"10.1007/s00424-025-03137-w","DOIUrl":"10.1007/s00424-025-03137-w","url":null,"abstract":"<p><p>Endometriosis (EM) is a common and challenging condition of reproductive-aged women and its pathogenesis is associated with endometrial stromal cells (ESCs). This study aimed to explore the role of FOXC1 in invasion and migration of ectopic ESCs (Ect-ESCs) in EM. Human eutopic and Ect-ESCs were isolated and identified, followed by detection of the levels of FOXC1, IGF2BP3, and m6A in ITGB1 in eutopic and Ect-ESCs. After interfering with FOXC1 in Ect-ESCs, cell invasion and migration were assessed. RNA immunoprecipitation assay was conducted to investigate the enrichment of IGF2BP3 or m6A on ITGB1. ITGB1 mRNA stability was examined. The roles of IGF2BP3 or ITGB1 in the invasion and migration of Ect-ESCs were verified by combined experiments. We found that FOXC1, IGF2BP3, and ITGB1 were upregulated in Ect-ESCs. FOXC1 downregulation inhibited invasion and migration of Ect-ESCs. Mechanically, FOXC1 bound to the IGF2BP3 promoter to positively regulate IGF2BP3 expression, promoted ITGB1 mRNA stability in an m6A-dependent manner, and increased ITGB1 transcription. Overexpression of IGF2BP3 or ITGB1 attenuated the inhibitory role of FOXC1 downregulation in invasion and migration of Ect-ESCs. In conclusion, FOXC1 promoted IGF2BP3 expression and stabilized ITGB1 mRNA in an m6A-dependent manner, thus promoting invasion and migration of Ect-ESCs.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"9"},"PeriodicalIF":3.2,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743524","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}
André Ivaniski-Mello, Alberto Enrico Minetti, Flávia Gomes Martinez, Leonardo Alexandre Peyré-Tartaruga
{"title":"An in-depth look at shallow-water walking: the mechanical determinants of the energy metabolic cost of shallow water walking in humans.","authors":"André Ivaniski-Mello, Alberto Enrico Minetti, Flávia Gomes Martinez, Leonardo Alexandre Peyré-Tartaruga","doi":"10.1007/s00424-025-03130-3","DOIUrl":"10.1007/s00424-025-03130-3","url":null,"abstract":"<p><p>Human locomotion in water involves unique forces (buoyancy, drag) influencing metabolic cost. However, a validated model integrating these forces to predict the cost of transport (COT) during shallow water walking (SWW) is lacking, and energetic optimization strategies remain unclear compared to terrestrial gaits. We measured the COT in nine healthy men during SWW across four immersion depths (knee to xiphoid) and four walking speeds (0.2-0.8 m/s). We developed and validated a physiomechanical model based on the mechanical work done against buoyancy-affected body weight and hydrodynamic drag. Using this model, we compared the energetics of SWW with swimming and dry land walking (including hypogravity conditions) and analyzed self-selected walking speeds. The minimum COT occurred at hip immersion depth (0.2 m/s), rather than at intermediate speeds, with the J-shaped relationship observed only at knee immersion depth. Metabolic power, in contrast, remained relatively constant during self-selected walking across immersion depths. An immersion depth threshold near the center of mass emerged, above which swimming becomes more economical than SWW. Our physiomechanical model accurately predicted the measured COT. The interplay between buoyancy and drag dictates SWW energetics, shifting optimization away from intermediate speeds common on dry land. From a physiological perspective, these findings quantify the energetic consequences of human locomotor adaptation to the unique mechanical challenges posed by aquatic environments. Furthermore, identifying an immersion depth threshold influencing the economical choice between walking and swimming provides new insights into human aquatic locomotor adaptations.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"7"},"PeriodicalIF":3.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12698785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743532","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}
Marvin J A Meyer, George Oprita, Tabea C Fricke, Inês Carvalheira Arnaut Pombei Stein, Frank G Echtermeyer, Christine Herzog, Andreas Leffler
{"title":"Lysophosphatidylcholine sensitizes TRPV2 by indirect mechanisms.","authors":"Marvin J A Meyer, George Oprita, Tabea C Fricke, Inês Carvalheira Arnaut Pombei Stein, Frank G Echtermeyer, Christine Herzog, Andreas Leffler","doi":"10.1007/s00424-025-03131-2","DOIUrl":"10.1007/s00424-025-03131-2","url":null,"abstract":"<p><p>The ion channel TRPV2 has multiple roles in immunology, cancer, cardiovascular function and pain signaling. However, only few endogenous modulators of TRPV2 have been described. The phospholipase A2 (PLA2)-derived lipid lysophosphatidylcholine (LPC) was demonstrated to induce pain and itch by activating sensory neurons, and it seems to be a direct agonist of TRPV4 and TRPC5. Although LPC was suggested to modulate TRPV2, the molecular mechanisms for this effect remain unclear. Here we used patch clamp and calcium imaging techniques to investigate if and how TRPV2 is modulated by LPC. Rat, mouse and human TRPV2 were not directly activated by LPC. Instead, 10 µM LPC induced a TRPV2-independent calcium influx and irreversible inward currents in HEK 293T cells. However, 3 µM LPC induced a reversible potentiation of membrane currents induced by 2-APB, cannabidiol (CBD), probenecid (PBC) and weak acids, but not to heat. This sensitization of TRPV2 was robust in whole cell experiments, but not in cell-free inside-out or outside-out patches. A disruption of the actin cytoskeleton with cytochalasin D, but also the depletion of cholesterol or sphingomyelin from the cell membrane diminished the potentiating effects of LPC on TRPV2. In conclusion, we present novel data describing that the PLA2 downstream signaling lipid LPC amplifies TRPV2-mediated responses via indirect mechanisms that seem to involve a destabilization of lipid rafts and the actin cytoskeleton.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"8"},"PeriodicalIF":3.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743520","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}
André Budrowitz, Mitko Mladenov, Hristo Gagov, Rudolf Schubert
{"title":"Differential effect of pulsatile pressure on the myogenic responses of small arteries.","authors":"André Budrowitz, Mitko Mladenov, Hristo Gagov, Rudolf Schubert","doi":"10.1007/s00424-025-03145-w","DOIUrl":"10.1007/s00424-025-03145-w","url":null,"abstract":"<p><p>The myogenic response is an important regulatory mechanism under physiological as well as pathophysiological conditions. However, little is known about the myogenic response under pulsatile pressure conditions. Therefore, based on the known mechanisms governing the myogenic response induced by static pressure, we tested the hypothesis that a stronger myogenic response induced by pulsatile pressure is due to a larger increase of the intracellular calcium concentration and/or a higher calcium sensitivity of vessel tone. Rat small tail and gracilis arteries were studied using isobaric myography and FURA-2 fluorimetry. We found that in small tail arteries, the effect of pulsatile pressure on the myogenic response is determined by its systolic pressure, whereas in gracilis arteries, the effect of pulsatile pressure is determined by its mean pressure. Interestingly, the effect of pulsatile pressure on the intracellular calcium concentration in both vessels is determined by its systolic pressure. However, while calcium sensitivity of myogenic tone did not differ between static and pulsatile pressure conditions in small tail arteries, it was weaker under pulsatile pressure than under static pressure in gracilis arteries. In conclusion, a stronger myogenic response under pulsatile pressure conditions, i.e., the capability of a vessel to respond to systolic pressure, requires the vessel's ability to maintain and not lose the calcium sensitivity of myogenic tone compared to static pressure conditions.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"6"},"PeriodicalIF":3.2,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12689833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715384","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":"From chaos to control: Nobel insights in regulatory T cells and immune tolerance.","authors":"Anna Estrada Brull, Nicole Joller","doi":"10.1007/s00424-025-03140-1","DOIUrl":"10.1007/s00424-025-03140-1","url":null,"abstract":"<p><p>The 2025 Nobel prize in Medicine or Physiology was awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi for unravelling the basis of peripheral immune tolerance: regulatory T (Treg) cells. Treg cells are a subset of CD4+ T helper cells characterized by the expression of the transcription factor Foxp3 and the surface receptor CD25 (IL-2 receptor alpha subunit) and are key for maintaining immune homeostasis and preventing autoimmunity. In this minireview, we trace the discovery of Treg cells, their phenotype and function and how these findings are employed in generating safer and more efficient therapies for autoimmune diseases and cancer.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"5"},"PeriodicalIF":3.2,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12689716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715463","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":"Hippocampal synaptic plasticity impairment and melatonin synthesis reduction in cognitive decline of a rodent model of Alzheimer's disease-like pathology.","authors":"Leila Karimi-Zandi, Samaneh Aminyavari, Maryam Zahmatkesh","doi":"10.1007/s00424-025-03134-z","DOIUrl":"10.1007/s00424-025-03134-z","url":null,"abstract":"<p><p>Melatonin, the pineal gland hormone, is produced in several extra-pineal tissues. The arylalkylamine N-acetyltransferase (AANAT) enzyme activity determines the overall rate of tissue melatonin synthesis. A decline in AANAT enzyme activity during acute amyloid-β (Aβ) neurotoxicity and reduced melatonin levels in Alzheimer's patients have been reported. These findings raise the question of whether brain melatonin synthesis is altered during cognitive decline. We investigated whether cognitive impairment induced by Aβ administration could affect the activation status of AANAT, a key hippocampal enzyme of melatonin synthesis. Male Wistar rats received intra-cerebroventricular Aβ injection. Two weeks after Aβ administration, the neuroinflammation was assessed by interleukin-1 (IL-1β) immunohistochemical staining. Hippocampal long-term potentiation (LTP) was evaluated using the technique of local field recording. The cognitive function was assessed using the Morris water maze behavioral test.The hippocampal AANAT activation status was assessed by Western blotting, and HPLC was used for melatonin level analysis. Aβ-induced spatial memory and LTP impairments were confirmed by increased escape latencies and alterations in the fEPSP slope. The Aβ provided a neuroinflammatory context, demonstrated by increased in the IL-1𝛽 staining. These alterations were accompanied by a reduction in the activation status of AANAT, as indicated by the p-AANAT/total AANAT ratio, in both the electrophysiology and behavioral experimental groups.These data suggest that the local activation status of AANAT may be contributed in the cognitive function of the hippocampus in a rodent model of cognitive decline induced by Aβ administration.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":"478 1","pages":"4"},"PeriodicalIF":3.2,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715419","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}