Pflugers Archiv : European journal of physiology最新文献_第2页

Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels. 对健康年轻男性进行有控制的饮食磷酸盐负荷可提高血浆磷酸盐和 FGF23 水平。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-11-27 DOI: 10.1007/s00424-024-03046-4

Jennifer Scotti Gerber, Eva Maria Pastor Arroyo, Johanne Pastor, Miguel Correia, Stefan Rudloff, Orson W Moe, Daniela Egli-Spichtig, Nilufar Mohebbi, Carsten A Wagner

{"title":"Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels.","authors":"Jennifer Scotti Gerber, Eva Maria Pastor Arroyo, Johanne Pastor, Miguel Correia, Stefan Rudloff, Orson W Moe, Daniela Egli-Spichtig, Nilufar Mohebbi, Carsten A Wagner","doi":"10.1007/s00424-024-03046-4","DOIUrl":"10.1007/s00424-024-03046-4","url":null,"abstract":"Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000 mg phosphorus equivalent/day) supplemented with either a phosphate binder (low Pi diet) or phosphate capsules (750 mg phosphorus, high Pi diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"495-508"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731753","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}

引用次数: 0

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction. 25-羟基胆固醇调节小鼠神经肌肉连接处突触囊泡内吞作用。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-09 DOI: 10.1007/s00424-024-03058-0

Eva A Kuznetsova, Guzalia F Zakirjanova, Andrei N Tsentsevitsky, Alexey M Petrov

{"title":"25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.","authors":"Eva A Kuznetsova, Guzalia F Zakirjanova, Andrei N Tsentsevitsky, Alexey M Petrov","doi":"10.1007/s00424-024-03058-0","DOIUrl":"10.1007/s00424-024-03058-0","url":null,"abstract":"Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability. Here, using fluorescent dyes, the time course of endocytosis induced by intense activity of the phrenic nerve was studied at the mouse diaphragm neuromuscular junction. It was found that a significant portion of endocytic events occurs after the end of tetanic stimulation. Pitstop 2, clathrin inhibitor, and more profoundly dynole 34-2, dynamin antagonist, suppressed endocytic FM1-43 dye uptake both during and after tetanus. Furthermore, synaptic vesicles formed in the presence of the endocytic blockers released FM-dye during subsequent evoked exocytosis at a lower rate. 25-Hydroxycholesterol (25HC) is an oxysterol, ubiquitously synthetized from excessive cholesterol. In addition, its production greatly increases by activated macrophages. 25HC accelerated FM-dye endocytosis and its sequential evoked exocytosis, and dynole (but not pitstop) prevented 25HC-mediated enhancement of endocytic FM-dye uptake. The positive effects of 25HC were interfered with chelation of cytosolic Ca2+ with a slow Ca2+ buffer EGTA-AM, Ca2+ antagonist TMB8, and sphingomyelin-hydrolyzing enzyme. In contrast to amphiphilic FM1-43 dye capture, 25HC reduced uptake of hydrophilic high molecular weight markers (labeled dextrans and toxin), which utilize bulk endocytosis to enter into nerve terminals. Thus, synaptic vesicle endocytosis had a relatively slow kinetics following the tetanic activity and can be accelerated by 25HC. The positive effect of 25HC on endocytosis engages a dynamin-dependent pathway, interconnected with cytoplasmic Ca2+ and sphingomyelin integrity.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"421-439"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953139","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}

引用次数: 0

Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential. tDCS对癫痫中谷氨酸能通路的影响：神经保护和治疗潜力。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-12-07 DOI: 10.1007/s00424-024-03049-1

Filiz Demirdogen, Guven Akcay

{"title":"Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential.","authors":"Filiz Demirdogen, Guven Akcay","doi":"10.1007/s00424-024-03049-1","DOIUrl":"10.1007/s00424-024-03049-1","url":null,"abstract":"Epilepsy is a chronic neurological disease characterized by recurrent seizures caused by abnormal electrical activity in the brain. The aim of our study was to investigate the effect of tDCS on oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in kindling-induced epilepsy model. Behavioral tests evaluated motor and cognitive functions, while assessing oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in hippocampal tissue. tDCS stimulation therapy demonstrates a neuroprotective effect on motor and cognitive function postepilepsy. Our study reveals an increase in TOC, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels and a decline in total antioxidant capacity (TAC) following PTZ-induced seizures. However, tDCS treatment led to a significant decrease of Ca2+, total oxidant capacity (TOC), glutamate, GABA, AMPAR1, and NMDAR1 levels in the epilepsy cohorts, while simultaneously causing a spike in TAC levels. The study's results showed that tDCS treatment could have a therapeutic effect on oxidative stress, Ca2+, TOC, glutamate, GABA, AMPAR1, NMDAR1, and TAC in both acute and chronic kindling epilepsy models.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"341-348"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791706","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}

引用次数: 0

The lateral habenula regulates stress-related respiratory responses via the monoaminergic system. 外侧哈文脑通过单胺能系统调节与压力有关的呼吸反应。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-11-19 DOI: 10.1007/s00424-024-03043-7

Riko Mizukami, Masayuki Matsumoto, Tadachika Koganezawa

{"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":"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 GABAA 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.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"441-452"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825555/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lateral hypothalamic area high-frequency deep brain stimulation rescues memory decline in aged rat: behavioral, molecular, and electrophysiological study. 下丘脑外侧区高频深部脑刺激恢复老年大鼠记忆衰退：行为学、分子和电生理研究。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1007/s00424-024-03059-z

Abdelaziz M Hussein, Ahmed F Abouelnaga, Walaa Obydah, Somaya Saad, Marwa Abass, Asmaa Yehia, Eman M Ibrahim, Ahmed T Ahmed, Osama A Abulseoud

{"title":"Lateral hypothalamic area high-frequency deep brain stimulation rescues memory decline in aged rat: behavioral, molecular, and electrophysiological study.","authors":"Abdelaziz M Hussein, Ahmed F Abouelnaga, Walaa Obydah, Somaya Saad, Marwa Abass, Asmaa Yehia, Eman M Ibrahim, Ahmed T Ahmed, Osama A Abulseoud","doi":"10.1007/s00424-024-03059-z","DOIUrl":"10.1007/s00424-024-03059-z","url":null,"abstract":"To examine the effect of DBS of the lateral hypothalamic area (LHA) on age-related memory changes, neuronal firing from CA1, oxidative stress, and the expression of Hsp70, BDNF, and synaptophysin. 72 male rats were randomly allocated into 6 equal groups: a) normal young group (8 W), b) sham young group, c) DBS young group, d) normal old group (24 months), e) sham old group and f) DBS old group. Memory tests (passive avoidance and Y maze), oxidative stress markers (MDA, catalase, and GSH) and expression of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin were measured by the end of the experiment. Also, in vivo recording of the neuronal firing of the CA1 region in the hippocampus was done. Old rats show significant decline in memories, antioxidant genes (Nrf2 and HO-1), antioxidants (GSH and catalase), Hsp70, BDNF, and synaptophysin with significant increase in MDA in hippocampus (p < 0.05) and DBS for LHA caused a significant improvement in memories in old rats, with significant rise in fast gamma and theta waves in CA1 region in old rats (p < 0.05). This was associated with a significant increase in antioxidants (GSH and CAT), antioxidant genes (Nrf2, HO-1), Hsp70, BDNF, and synaptophysin with significant reduction in MDA in hippocampus (p < 0.05). DBS for LHA ameliorates the age-induced memory decline. This might be due to increase in fast gamma in CA1, attenuation of oxidative stress, upregulation of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin in the hippocampus.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"371-391"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009876","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}

引用次数: 0

Obituary: Stefan Silbernagl - physiologist, gentleman, aesthete.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-28 DOI: 10.1007/s00424-025-03070-y

Michael Gekle

引用次数: 0

Current methods in explainable artificial intelligence and future prospects for integrative physiology.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-25 DOI: 10.1007/s00424-025-03067-7

Bettina Finzel

引用次数: 0

Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-18 DOI: 10.1007/s00424-025-03069-5

Sandra Hummelgaard, Jean-Claude Kresse, Michael Schou Jensen, Simon Glerup, Kathrin Weyer

{"title":"Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.","authors":"Sandra Hummelgaard, Jean-Claude Kresse, Michael Schou Jensen, Simon Glerup, Kathrin Weyer","doi":"10.1007/s00424-025-03069-5","DOIUrl":"https://doi.org/10.1007/s00424-025-03069-5","url":null,"abstract":"Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD). Key features of CKD include proteinuria and reduced glomerular filtration rate, both of which are linked to disease progression and adverse outcomes. Dyslipidemia, a major CVD risk factor, often correlates with CKD severity and is inadequately addressed by conventional therapies. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in lipid metabolism by modulating low-density lipoprotein receptor (LDLR) levels and has emerged as a therapeutic target for managing dyslipidemia. PCSK9 inhibitors, including monoclonal antibodies and siRNA, effectively lower LDL cholesterol levels and have demonstrated safety in patients with mild to moderate CKD. Recent findings indicate that PCSK9 aggravates proteinuria by interacting with and downregulating megalin, a proximal tubule receptor essential for protein reabsorption in the kidney. Inhibition of PCSK9 has been shown to preserve megalin levels, reduce proteinuria, and improve the disease phenotype in experimental models. However, conflicting data from preclinical studies underscore the need for further research to clarify the mechanisms underlying PCSK9's role in kidney disease. This review highlights the potential of PCSK9 inhibition in addressing proteinuria and dyslipidemia in CKD, emphasizing its promise as a therapeutic strategy, while addressing current challenges and future directions for research.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441701","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}

引用次数: 0

The obesity pandemic and its impact on non-communicable disease burden.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-10 DOI: 10.1007/s00424-025-03066-8

Staffan Hildebrand, Alexander Pfeifer

引用次数: 0

Sphingosine kinase 1 inhibition aggravates vascular smooth muscle cell calcification.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-03 DOI: 10.1007/s00424-025-03068-6

Mehdi Razazian, Sheyda Bahiraii, Isratul Jannat, Adéla Tiffner, Georg Beilhack, Bodo Levkau, Jakob Voelkl, Ioana Alesutan

{"title":"Sphingosine kinase 1 inhibition aggravates vascular smooth muscle cell calcification.","authors":"Mehdi Razazian, Sheyda Bahiraii, Isratul Jannat, Adéla Tiffner, Georg Beilhack, Bodo Levkau, Jakob Voelkl, Ioana Alesutan","doi":"10.1007/s00424-025-03068-6","DOIUrl":"https://doi.org/10.1007/s00424-025-03068-6","url":null,"abstract":"Medial vascular calcification is common in chronic kidney disease patients and linked to hyperphosphatemia. Upon phosphate exposure, intricate signaling events orchestrate pro-calcific effects in the vasculature mediated by vascular smooth muscle cells (VSMCs). Sphingosine kinase 1 (SPHK1) produces sphingosine-1-phosphate (S1P) and is associated with complex effects in the vascular system. The present study investigated a possible involvement of SPHK1 in VSMC calcification. Experiments were performed in primary human aortic VSMCs under pro-calcific conditions, with pharmacological inhibition or knockdown of SPHK1 or SPNS2 (a lysolipid transporter involved in cellular S1P export), as well as in Sphk1-deficient and wild-type mice treated with cholecalciferol. In VSMCs, SPHK1 expression was up-regulated by pro-calcific conditions. Calcification medium up-regulated osteogenic marker mRNA expression and activity as well as calcification of VSMCs, effects significantly augmented by co-treatment with the SPHK1 inhibitor SK1-IN-1. SK1-IN-1 alone was sufficient to up-regulate osteogenic signaling in VSMCs during control conditions. Similarly, the SPHK1 inhibitor PF-543 and SPHK1 knockdown up-regulated osteogenic signaling in VSMCs and aggravated VSMC calcification. In contrast, co-treatment with the SPNS2 inhibitor SLF1081851 suppressed osteogenic signaling and calcification of VSMCs, effects abolished by silencing of SPHK1. In addition, Sphk1 deficiency aggravated vascular calcification and aortic osteogenic marker expression in mice after cholecalciferol overload. In conclusion, SPHK1 inhibition, knockdown, or deficiency aggravates vascular pro-calcific signaling and calcification. The reduced calcification after inhibition of S1P export suggests a possible involvement of intracellular S1P, but further studies are required to elucidate the complex roles of SPHKs and S1P signaling in calcifying VSMCs.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080789","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}

引用次数: 0