Pflugers Archiv : European journal of physiology最新文献

{"title":"The relevance of RNA-DNA interactions as regulators of physiological functions.","authors":"Julia Stötzel, Timothy Warwick, Praveenya Tirunagari, Ralf P Brandes, Matthias S Leisegang","doi":"10.1007/s00424-025-03091-7","DOIUrl":"10.1007/s00424-025-03091-7","url":null,"abstract":"<p><p>RNA-DNA interactions are fundamental to cellular physiology, playing critical roles in genome integrity, gene expression, and stress responses. This review highlights the diverse structures of RNA-DNA hybrids, including R-loops, RNA-DNA triplexes, and RNA-DNA hybrid G-quadruplexes (hG4s) and their relevance in physiology. R-loops are formed during transcription and replication, which regulate gene expression and chromatin dynamics but can also threaten genome stability. RNA-DNA triplexes, often formed by long noncoding RNAs (lncRNAs) such as FENDRR and MEG3, recruit chromatin modifiers like Polycomb repressive complex 2 to modulate gene expression, influencing organogenesis and cell specification. hG4s, formed by guanine-rich sequences in RNA and DNA, regulate transcription termination and telomere stability. Through this, hG4s can affect gene suppression and replication regulation. RNA-DNA hybrids are tightly regulated by helicases, RNase H enzymes, and topoisomerases, with altered regulation linked to genomic instability and disease. This review discusses the complexity of RNA-DNA interactions and their recently identified contributions to cellular physiology.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"889-901"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111601","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":"SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.","authors":"Benedikt Fels, Felix Fischer, Lisbeth Herrnboeck, David Beckers, Leon Niedzielski, Paul Roche, Alexandra Straeter, Ioana Alesutan, Johanna-Theres Borutta, Frederic Jaisser, Olivier Staub, Jakob Voelkl, Kristina Kusche-Vihrog","doi":"10.1007/s00424-025-03093-5","DOIUrl":"10.1007/s00424-025-03093-5","url":null,"abstract":"<p><p>The endothelial ENaC (EnNaC) is mainly responsible for maintaining the mechanical properties of the endothelial cell surface, the sensitivity to the shear forces of the streaming blood and thus for vascular function. The correlation between EnNaC surface expression, the dynamics of the actin cortex, the mechanical stiffness, and nitric oxide release indicates a close structure-function relationship. Mechanical flexibility of the endothelial surface has been associated with proper vascular function, while chronic stiffening leads to endothelial dysfunction and the so-called 'stiff endothelial cell syndrome' (SECS). With the help of atomic force microscopy (AFM)-based nanoindentation and immunofluorescence staining in vitro and ex vivo, we investigated the underlying cellular mechanisms and signalling pathways of EnNaC-dependent endothelial behaviour. We were able to show that the interaction between EnNaC and the cortical cytoskeleton is mediated by the small GTPases RhoA, Rac1, and the Arp2/3 complex. The functional inhibition of EnNaC by the drugs amiloride and benzamil led to membrane removal of the channel within minutes. Furthermore, we could observe an involvement of mineralocorticoid receptor, SGK1 and Nedd4-2 in regulation of endothelial cell stiffness. Our study contributes further insights on complex regulation of EnNaC and elucidates its interaction with the actin cytoskeleton, which could be central to its role as a key regulator of vascular function in health and disease.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"977-992"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120514","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":"Thermosensitivity of TREK K2P channels is controlled by a PKA switch and depends on the microtubular network.","authors":"Sönke Cordeiro, Marianne Musinszki","doi":"10.1007/s00424-025-03089-1","DOIUrl":"10.1007/s00424-025-03089-1","url":null,"abstract":"<p><p>Temperature sensing is an essential component of animal perception and enables individuals to avoid painful or lethal temperatures. Many temperature sensors in central and peripheral neurons are ion channels. Here, we focus on the thermosensitive TREK/TRAAK subfamily of K2P channels-the only known K⁺ selective thermosensitive channels. The C-terminal domain is essential for the temperature activation of TREK channels, but the mechanism of temperature sensation and the nature of the temperature sensor are unknown. We studied the thermosensitivity of representatives of all K2P channel subfamilies and identified TREK-1 and TREK-2 as the only thermosensitive K2P channels, while TRAAK, the third member of the mechano-gated subfamily, showed no temperature dependence. We transferred the thermosensitivity of TREK-1 to TRAAK channels by exchanging the C-termini, demonstrating that the C-terminal domain is sufficient to confer thermosensitivity. By gradually truncating the C-terminus, we isolated a specific temperature responsive element (TRE) consisting of 18 amino acids that constitutes a unique feature in mammalian thermosensitive channels. Within this TRE lie both the binding domain for microtubule associated protein 2 (MAP2) and the PKA phosphorylation site. Pharmacological disruption of the microtubular network as well as the loss of the MAP2 binding site suppressed the temperature response, and PKA activation completely abolished temperature sensitivity. Thus, the connection to the microtubular network enables the thermosensitivity of TREK channels, which is not intrinsic to the channel itself, while the PKA-mediated phosphorylation status acts as a switch that determines if TREK channels are thermosensitive at all.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"953-966"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079403","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 crucial decade that ion channels were proven to exist : The vision of Bertil Hille and Clay Armstrong and how it came through.","authors":"Luigi Catacuzzeno, Antonio Michelucci, Fabio Franciolini","doi":"10.1007/s00424-025-03085-5","DOIUrl":"10.1007/s00424-025-03085-5","url":null,"abstract":"<p><p>This retrospective begins with the first recording of the Na⁺ and K⁺ currents underlying the action potential in the squid giant axon reported by Hodgkin and Huxley in 1952, which made the question of where ions pass through the membrane more compelling. The notion of channels in the membrane had been around for quite some time but was so vague and contested that even the recording of Na⁺ and K⁺ currents through the membrane was not considered sufficient proof of their existence. In fact, Hodgkin and Huxley never referred to ion channels in their papers, only currents and conductances. The word \"channel\" remained somewhat left out from the scientific debate for almost another two decades, even though its idea was slowly making its way into the minds of discerning scientists. It is precisely this period that the present retrospective focuses on to understand the evolution of the ion channel concept from a speculative functional entity to a physical transmembrane object that serves the efficient and selective passage of ions. In this regard, the fundamental contribution of Bertil Hille and Clay Armstrong in promoting this idea, in the cold attitude, when not open aversion, of much of the scientific community, is fully acknowledged. Mention should also be made of Erwin Neher and Bert Sakmann's patch-clamp technique, which made it possible to directly measure ion currents through individual channels, thus conclusively demonstrating their presence in cell membranes. The retrospective goes on to briefly show how the cloning of ion channels in the 1980s and the first X-ray crystallographic structures at the turn of the century fully confirmed the initial suggestions, and closes by illustrating the relevance of ion channels in biology and medicine.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"903-917"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027519","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":"Creatine monohydrate supplementation and NOX impact skeletal muscle microvascular blood flow: a pilot study.","authors":"Paul A Baker, Holly E Clarke, Cesar A Meza, Mostafa M Ali, Robert C Hickner","doi":"10.1007/s00424-025-03090-8","DOIUrl":"10.1007/s00424-025-03090-8","url":null,"abstract":"<p><p>Impaired blood flow and elevated reactive oxygen species (ROS) concentrations, generated primarily from NADPH oxidase (NOX), indicate risk for cardiovascular disease (CVD). Creatine monohydrate (CM) may reduce CVD risk by lowering ROS concentrations and increasing skeletal muscle microvascular blood flow (SMBF). To determine if NOX-derived ROS impairs SMBF and whether five days of CM supplementation reduces in-vivo ROS concentrations and improves SMBF. Seven individuals had two microdialysis probes placed (control (CON) and apocynin (APO): NOX inhibitor) in skeletal muscle to measure in-vivo ROS (Hydrogen Peroxide (H₂O₂)) concentrations and SMBF (ethanol outflow/inflow ratio, inversely related to blood flow) at rest and four hours post-meal consumption. Procedures were performed before (PRE) and after (POST) five days of CM supplementation (20 g/day). Dialysate H₂O₂ concentrations were lower in the APO probe compared to CON from 120-140 min (APO: 1.19 ± 0.39 µM; CON: 2.04 ± 0.95 µM, p = 0.039), 140-160 min (APO: 1.17 ± 0.37 µM; CON: 2.06 ± 0.98 µM, p = 0.034) and 160-180 min post meal ingestion (p ≤ 0.05). APO perfusion increased SMBF at 20-40 min, 120-140 min (APO: 0.61 ± 0.13; CON: 0.75 ± 0.09 µM, p = 0.048), 140-160 min (APO: 0.61 ± 0.12 µM; CON: 0.76 ± 0.14 µM, p = 0.046), 160-180 min, and 180-200 min post meal (p ≤ 0.05). Ethanol outflow/inflow ratio was lower (higher SMBF) POST CM supplementation compared to PRE CM supplementation at 0-20 min (p = 0.036) and 20-40 min (p = 0.049) following HC/HF meal consumption. Inhibition of NOX-derived ROS increased SMBF, suggesting that NOX activity may impair blood flow regulation over the duration of baseline and post-prandial time points. Further, CM supplementation could be an effective strategy for enhancing postprandial blood flow.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"967-976"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187598","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":"Characterization of ROMK cellular heterogeneity along the mouse kidney thick ascending limb.","authors":"Christian Keller, Rui Ramos Santos, Wouter H van Megen, Johannes Loffing","doi":"10.1007/s00424-025-03086-4","DOIUrl":"10.1007/s00424-025-03086-4","url":null,"abstract":"<p><p>The renal thick ascending limb (TAL) plays a key role in water and ion homeostasis. Apical potassium secretion via the renal outer medullary potassium channel (ROMK) is essential for transepithelial sodium reabsorption via the furosemide-sensitive Na-K-2Cl-cotransporter and creates the electrochemical gradient for paracellular ion transport through Claudin tight junction proteins. Interestingly, the TAL exhibits transcriptomic heterogeneity and variable apical ROMK abundance. Single-cell RNA sequencing suggests that the cortical TAL consists of at least three distinct cell types, but whether ROMK distribution aligns with these types remains unclear. We analyzed perfusion-fixed mouse kidneys using RNAscope in situ hybridization (ISH), iterative indirect immunofluorescence imaging (4i multiplexing), and machine learning. ROMK mRNA expression was seen in all TAL cells. In contrast, apical ROMK protein abundance was found on almost all macula densa (MD) cells but was heterogeneous along the rest of the TAL. In the remaining TAL, only about 60% of the TAL cells had strong apical ROMK staining, while 40% lacked apical ROMK but showed weak perinuclear signals. ISH revealed that apical ROMK-positive cells express Ptger3 mRNA, whereas apical ROMK-negative cells express Foxq1 mRNA. Multiplexing analysis showed that ROMK-positive cells form Claudin-10b-positive tight junctions, while ROMK-negative cells form Claudin-16/19-positive junctions and express basolateral Kir4.1. Despite universal ROMK mRNA expression, apical ROMK distribution aligns with molecularly distinct TAL cell types. This unique ROMK expression pattern suggests functional heterogeneity for ROMK along the TAL.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"841-856"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985924","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":"Inhibition of Rho-kinase by fasudil contributes to the modulation of the synaptic plasticity response in the rat hippocampus.","authors":"Ercan Babur, Hatice Saray, Cem Süer, Nurcan Dursun","doi":"10.1007/s00424-025-03078-4","DOIUrl":"10.1007/s00424-025-03078-4","url":null,"abstract":"<p><p>Metaplasticity refers to an activity-dependent change in the physiological or biochemical state of neurons that changes their ability to generate subsequently induced synaptic plasticity, such as long-term potentiation (LTP) or long-term depression (LTD). Rho-kinases (ROCK) are known to be important for stable changes in synaptic strength, especially LTP. In this study, we investigated whether LTP inhibition in synapses primed with 1-Hz stimulation was affected by ROCK inhibition in young adult male rats. The study also examined the pattern of tau phosphorylation that occurs during metaplastic regulation, applying into perspective the phosphorylation of tau protein by ROCK. Field potentials consisting of an excitatory postsynaptic potential (fEPSP) and population spike (PS) were recorded from the granule cell layer of the hippocampal dentate gyrus (DG). Metaplastic LTP was induced by strong tetanic stimulation (HFS) of the lateral perforant path after a low-frequency stimulation (LFS) protocol. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record fEPSP and drug infusion. Drug infusion (saline, n = 8; fasudil, n = 8, 10 µM) was started after the 15-min baseline recording and lasted for 60 min. Total and phosphorylated tau levels were measured in the stimulated hippocampus, which was immediately removed after the electrophysiological recording. LFS prevented the induction of LTP in response to HFS and even produced synaptic LTD in the saline-infused group (83.8 ± 2.6% of the baseline), but moderate potentiation of fEPSP (121.1 ± 7.7% of the baseline) occurred at the end of recording in the experiments where fasudil infusion was performed. LFS caused a comparable early depression, and HFS resulted in a comparable potentiation of the PS amplitude in both groups. Granular cells of the DG failed to exhibit synaptic LTP inhibition in the presence of fasudil, and levels of total and phosphorylated GSK-3β and levels of phosphorylated tau (Ser³⁹⁶ and Ser²⁰²-Thr²⁰⁵) were found to be lower than those of the control group. Based on these findings, it can be concluded that pharmacological inhibition of ROCK results in impaired ability of dentate gyrus neurons to inhibit synaptic LTP, and this result is accompanied by decreased phosphorylation of GSK-3β and tau proteins. The negative effect of fasudil on neuronal function should not be neglected when evaluating its effects as a therapeutic agent for diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"787-796"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037466","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":"Impact of aldosterone deficiency on the development of diuretic resistance in mice.","authors":"Daniel Essigke, M Zaher Kalo, Andrea Janessa, Bernhard N Bohnert, Xiaqing Li, Andreas L Birkenfeld, Ferruh Artunc","doi":"10.1007/s00424-025-03082-8","DOIUrl":"10.1007/s00424-025-03082-8","url":null,"abstract":"<p><p>The effect of diuretics can be limited by stimulation of counter-regulatory mechanisms, eventually leading to diuretic resistance. It is thought that the mineralocorticoid aldosterone might contribute to the development of diuretic resistance. To test this, we challenged genetically modified mice with or without a deletion of the gene coding for the aldosterone synthase (AS) with furosemide, hydrochlorothiazide (HCT) and triamterene. Urinary excretion was studied in metabolic cages; kidneys were studied for expression of sodium transporters. In both genotypes, a 4-day treatment with HCT via drinking water (400 mg/l) induced a similar natriuresis and modest loss of body weight < 10%. In contrast, furosemide (125 mg/l) and triamterene (200 mg/l) via drinking water stimulated a significantly higher natriuresis and body weight loss in AS^-/- mice and in addition, triamterene caused massive hyperkalemia > 9 mM and acidosis (pH < 7.0). In AS^+/+ mice, plasma aldosterone concentration tended to increase under furosemide and HCT administration, while triamterene induced a robust ~ sixfold increase. In the kidney, apical targeting and proteolytic activation of the epithelial sodium channel ENaC were stimulated in AS^+/+ mice under triamterene treatment, an effect that was diminished in AS^-/- mice. In conclusion, aldosterone is essentially involved in the development of diuretic resistance to ENaC blockade by triamterene and to a lesser extent to furosemide. In contrast, resistance to HCT was independent of aldosterone.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"827-840"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041408","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":"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":"10.1007/s00424-025-03069-5","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"773-786"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","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}

{"title":"Probiotic Bactolac alleviates depression-like behaviors by modulating BDNF, NLRP3 and MC4R levels, reducing neuroinflammation and promoting neural repair in rat model.","authors":"Musab Işık, Fadime Köse, Özcan Budak, Cansu Özbayer, Rumeysa Keleş Kaya, Sevda Aydın, Aleyna Ceren Küçük, Mehmet Arif Demirci, Songül Doğanay, Cahit Bağcı","doi":"10.1007/s00424-025-03084-6","DOIUrl":"10.1007/s00424-025-03084-6","url":null,"abstract":"<p><p>Depression, a prevalent psychiatric disorder, exerts severe and debilitating impacts on an individual's mental and physical well-being, and it is considered a chronic mental illness. Chronic stress plays an important role in the pathophysiology of depression. Lactobacillus plantarum and Streptococcus thermophilus are psychobiotic bacteria and synthesize some neurotransmitters that play a role in the pathogenesis of depression. In this study, we aimed to investigate the therapeutic effects of Bactolac (Lactobacillus plantarum NBIMCC 8767  + Streptococcus thermophilus NBIMCC 8258) on chronic stress-induced depression in rats. Behavioral tests, including the sucrose preference test, elevated plus maze test, forced swim test, and three-chamber sociability test, were employed to assess depressive and anxiety-like behaviors. The expression level of the 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1, NLRP3 and MC4R; BDNF levels, glial activity and intestinal permeability were determined in chronic stress-induced depression in rats. In conclusions, chronic stress decreased the expression levels of 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1 and BDNF level; increased the expression levels of NLRP3 and MC4R, caused neurodegeneration and glial activity, ultimately led to depressive effects. Bactolac was effective in reducing depressive-like behaviors according to the results of behavioral tests. Bactolac treatment provided high neuronal survival rate increasing BDNF level, prevented the excessive release of pro-inflammatory cytokines by reducing the expression levels of NLRP3 and MC4R, therefore, prevented the excessive activation of the hypothalamus-pituitary-adrenal (HPA) axis and accordingly, reduced neurodegeneration and glial cell activation in depressed rats. We can suggest that Bactolac supplementation may be beneficial in coping with stress, alleviate the effects of chronic stress and help to protect mental health.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"797-814"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064372","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}