Frontiers in Physiology最新文献

{"title":"High-resolution analyses of the secretomes from murine C2C12 cells and primary human skeletal muscle cells reveal distinct differences in contraction-regulated myokine secretion.","authors":"Pia Marlene Förster, Julian Hogenkamp, Moira Fee Pottgießer, Christian Binsch, Awovi Didi Humpert, Carolin Laura Brügge, Michelle Isabel Deatc, Regina Ensenauer, Alexandra Chadt, G Hege Thoresen, D Margriet Ouwens, Sonja Hartwig, Stefan Lehr, Hadi Al-Hasani","doi":"10.3389/fphys.2025.1549316","DOIUrl":"https://doi.org/10.3389/fphys.2025.1549316","url":null,"abstract":"<p><p>Myokines released by skeletal muscle in response to contraction may contribute to the health-promoting effects of exercise. Previous studies with cultured rodent and human myotubes have revealed highly complex patterns of myokine secretion. However, the commonalities and differences in the secretory response of the different cell models have not been explored, limiting the interpretation of these results. In the present study, we performed a comprehensive analysis of contraction-regulated secretomes using the most commonly used skeletal muscle cell models, cultured murine C2C12 myotubes and satellite cell-derived primary human myotubes (HSkMC). The cells were subjected to low-frequency electrical pulse stimulation (EPS) for 6 h followed by high-resolution mass spectrometry analysis of secreted proteins in the culture medium. We identified 5,710 and 3,285 proteins in the secretomes of C2C12 myotubes and HSkMC, with 80% of human myokines also detected in the murine secretome. Additionally, we found 518 and 336 secreted proteins that were differentially regulated during contraction in murine and human cells, respectively, along with 1,440 and 385 previously unknown potential myokines secreted by murine and human myotubes. Bioinformatic prediction analyses revealed that the majority of the newly identified myokines were secreted via unconventional protein secretion pathways (UPS) in the murine secretome, whereas most novel proteins in the human secretome were secreted via the classical endoplasmic reticulum (ER)-to-Golgi pathway. Moreover, ontology analysis indicates cell type-specific differences in cellular compartments involved in myokine secretion. Collectively, our results provide a comprehensive overview of the secretomes of two of the most commonly used cell models and may provide guidance for further studies of myokines.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1549316"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic preconditioning: exploring local ergogenic mechanisms in non-fatiguing voluntary contractions.","authors":"Ruben Allois, Raffaele Pertusio, Pasquale Pagliaro, Silvestro Roatta","doi":"10.3389/fphys.2025.1542394","DOIUrl":"https://doi.org/10.3389/fphys.2025.1542394","url":null,"abstract":"<p><strong>Background: </strong>IPC has been suggested to boost skeletal muscle performance, though its effectiveness remains controversial. This study evaluates whether IPC influences local hemodynamic responses and surface electromyographic (sEMG) activity during non-fatiguing voluntary sustained and intermittent contractions.</p><p><strong>Methods: </strong>Ten male participants were subjected to IPC (3 cycles, 5-min ON/5-min OFF right arm ischemia, cuff pressure: 250 mmHg) and SHAM (same protocol at 20 mmHg) in two different sessions. Near-infrared spectroscopy was used to monitor tissue oxygenation (TOI) and deoxy-hemoglobin (HHb) in extensor and flexor forearm muscles. sEMG was also recorded. Measurements were taken during sustained (20-s duration) and intermittent (5 s ON/5 s OFF) isometric contractions at 20, 30, and 40% of the maximal voluntary contraction. These non-fatiguing exercise tasks were performed before and 30 min after the IPC/SHAM intervention.</p><p><strong>Results: </strong>sEMG exhibited a significant increase post vs. pre-treatment in both IPC and SHAM in extensors. A significant decrease in TOI at rest was noted pre vs. post-treatment for both IPC and SHAM (p < 0.01). In general, no main effect of treatment was observed, except for HHb changes during contraction in extensor muscles, associated with no effect of time and no time-treatment interaction. All variables exhibited a main effect of force level (p < 0.05), with no interaction with treatment or time.</p><p><strong>Conclusion: </strong>IPC had no effect on hemodynamic and electromyographic variables during sustained and intermittent handgrip. These results do not support IPC-related ergogenic effects at the muscle level, aligning with previous findings on electrically stimulated contractions.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1542394"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shape of the mitral annulus in normal individuals and dilated cardiomyopathies: computational modeling insights into leaflet stress distribution.","authors":"Salvatore Pasta, Eluisa La Franca, Fabrizio Crascì, Giovanni Gentile, Manlio Cipriani, Francesco Fulvio Faletra","doi":"10.3389/fphys.2025.1532972","DOIUrl":"https://doi.org/10.3389/fphys.2025.1532972","url":null,"abstract":"<p><p><b>Introduction:</b> The mitral valve annulus naturally adopts a saddle shape in systole, likely concentrating systolic stress on the commissures where fibrous trigones are located. This study hypothesized that in patients with dilated cardiomyopathies, where the annulus is large and planar, the stress would be redirected. <b>Methods:</b> Computational modeling was employed to compare the stress distribution in saddle-shaped mitral valves (n.10 patients) with planar annuli seen in dilated cardiomyopathy (n.10 patients) using kinematics of the mitral valve annulus from systole to diastole extrapolated from computed tomography angiography. <b>Results:</b> Simulations revealed high stress near the anterolateral and posteromedial commissures in normal valves, in contrast to high leaflet stress in planar annuli. Significant differences in stress distribution were observed near the anterolateral (S = 0.427 ± 0.053 MPa in normal valves vs S = 0.211 ± 0.123 MPa in diseased valves, p < 0.001) and posterolateral commissures (S = 0.340 ± 0.008 MPa in normal valves vs S = 0.208 ± 0.060 MPa in diseased valves, p < 0.001). Additionally, mitral annulus disjunction was present in healthy patients but absent in those with annulus planarity due to dilated cardiomyopathy. <b>Discussion:</b> This study suggests that while the saddle-shaped annulus focuses leaflet stress on commissures, planar annuli distribute systolic stress over leaflet surfaces. This may trigger embryonic pathways and alter mitral leaflet collagen content, ultimately leading to valve remodeling. Identifying patients with early annular planarity prior to substantial leaflet remodeling may provide early treatments to prevent increasing mitral regurgitation.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1532972"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue loss during neoadjuvant chemotherapy: a key prognostic factor in advanced epithelial ovarian cancer.","authors":"Wassim Benouali, Adeline Dolly, Aurore Bleuzen, Stéphane Servais, Jean-François Dumas, Christophe Vandier, Caroline Goupille, Lobna Ouldamer","doi":"10.3389/fphys.2025.1537484","DOIUrl":"https://doi.org/10.3389/fphys.2025.1537484","url":null,"abstract":"<p><strong>Background: </strong>Advanced epithelial ovarian cancer (EOC) patients often receive neoadjuvant platinum-based chemotherapy (NAC), with interval surgery (after three cycles of chemotherapy) considered as a major prognostic factors. We examined how changes in body composition (muscle and adipose tissue) during NAC influence prognosis.</p><p><strong>Objective: </strong>Using CT images acquired before and during NAC in a cohort of women with advanced EOC, the aim of this study was to analyze body composition (muscle and fat mass) and see whether these parameters, at diagnosis or as they evolve during chemotherapy, can be linked to recurrence-free survival and overall survival (RFS and OS).</p><p><strong>Material and methods: </strong>The study included 53 patients with FIGO stage III-IV epithelial ovarian cancer. CT images were analyzed to calculate skeletal muscle index (SMI), subcutaneous adipose tissue index visceral adipose tissue index estimated lean body mass (LBM) and estimated whole-body fat mass (WFM). Changes in tissue composition were normalized for 100 days and expressed as % change to account for intervals between scans at baseline and after three cycles of chemotherapy. The impact on survival was assessed by Log-rank test.</p><p><strong>Results: </strong>At diagnosis, clinical criteria such as age or BMI did not correlate with RFS or OS. 60% of patients were considered sarcopenic (low SMI), including mainly underweight and normal-weight patients. Low SMI was not associated with RFS or OS. Twenty-six patients who underwent interval surgery demonstrated longer relapse-free intervals (<i>p</i> = 0.01). Notably, while muscle parameters showed minimal changes (-2%), parameters assessing adipose tissue showed significant decreases of 10, 12% and 7.6% per 100 days (VATI, SATI and estimated WFM, respectively). Obese patients were particularly affected by this loss of muscle and fat, compared with patients in other BMI categories. Rapid and severe loss of VATI (-28% per 100 days) and estimated WFM (-18% per 100 days) were significantly associated with shorter OS (<i>p</i> = 0.031 and <i>p</i> = 0.046 respectively).</p><p><strong>Conclusion: </strong>Our findings suggests that early and substantial loss of visceral adipose tissue during NAC is a significant predictor of poor survival in advanced EOC. This highlights an urgent need for targeted nutritional or pharmaceutical strategies to mitigate fat loss and improve patients outcomes.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1537484"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into athlete physical recovery concerning lactate metabolism, lactate clearance and fatigue monitoring: A comprehensive review.","authors":"Tianhao Huang, Zeyu Liang, Ke Wang, Xiangjun Miao, Lei Zheng","doi":"10.3389/fphys.2025.1459717","DOIUrl":"https://doi.org/10.3389/fphys.2025.1459717","url":null,"abstract":"<p><p>Lactate accumulation will appear in athlete skeletal muscle after intense exercise. If the high lactate level maintains, athletes will sustain fatigue and athletic capacity decline due to internal environment and normal metabolism disruption. In order to enhance athlete physical recovery and exercise performance in high-intensity sport events, it is of great significance to explore the scientific intervention procedures based on quicker lactate clearance in skeletal muscle and blood after exercise. This article collects classic and novel literature in terms of lactate metabolism, lactate clearance and fatigue monitoring during exercise by searching PubMed database and then summarizes comprehensive insights into athlete physical recovery with corresponding figures and charts. We introduce the generation and transformation process of lactate, lactate clearance pathways and the fatigue monitoring methods for athletes in detail. The lactate clearance pathways involve biochemical pathways (oxygen inhalation, amino acids supplement, targeting free radical, alkaline reserve, targeting vasomotion, ribose supplement), physical activities (exercise-mediated activities, non-exercise activities) and training methods (interval training, altitude training) to accelerate lactate metabolism. The biochemical factors for monitoring athletic fatigue level involve blood, urine, sweat, saliva and exhaled gas. We hope this review can offer some significant and scientific assistance for athlete recovering after exercise and improving sport achievements based on quicker lactate clearance.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1459717"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Emerging topics in human physiology.","authors":"Joaquín García-Estañ López, Ginés Viscor, Luis Monteiro Rodrigues","doi":"10.3389/fphys.2025.1594305","DOIUrl":"https://doi.org/10.3389/fphys.2025.1594305","url":null,"abstract":"","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1594305"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on optimal strategy of different fire rescue tasks based on oxygen consumption.","authors":"Jinyong Tang, Xinxin Zhang, Ziwen Wang, Tiehuai Liang, Weiguo Liu","doi":"10.3389/fphys.2025.1548031","DOIUrl":"10.3389/fphys.2025.1548031","url":null,"abstract":"<p><strong>Objective: </strong>The development of effective rescue strategies is critical for enhancing rescue operations and ensuring firefighter safety. However, limited attention has been given to the exploration of rational rescue strategies in practice, particularly with regard to oxygen consumption. Therefore, this study aimed to identify the optimal rescue strategy by analyzing oxygen consumption across different rescue tasks.</p><p><strong>Methods: </strong>Sixty male firefighters from the Guilin Fire and Rescue Detachment participated in the study. Their oxygen consumption was measured during the completion of running on flat ground and while running up and down three flights of stairs.</p><p><strong>Results: </strong>The results found that firefighters with excellent strength and conditioning levels, those carrying a 10 kg load, or those employing the shoulder-carrying technique had less oxygen consumption. Hand-carrying for a 10 kg load when running up or downstairs and shoulder-carrying for 20 and 30 kg loads while running on the ground resulted in lower oxygen consumption. Additionally, firefighters with excellent strength performance when running with 10 and 20 kg loads or those with excellent speed while running on the ground exhibited decreased oxygen consumption.</p><p><strong>Conclusion: </strong>The current study suggests that firefighters with excellent strength performance are more suited for upstairs rescue tasks, while those with excellent speed performance are better suited for tasks on ground. It is recommended that medium to large loads be carried using the shoulder-carrying technique, and smaller loads be hand-carried when running up or down stairs. Overall, customizing rescue strategies based on firefighters' strength and conditioning, load characteristics, techniques, and specific task requirements is crucial for improving efficiency and reducing risks in rescue operations.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1548031"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced thyroid nodule detection and diagnosis: a mobile-optimized DeepLabV3+ approach for clinical deployments.","authors":"Changan Yang, Muhammad Awais Ashraf, Mudassar Riaz, Pascal Umwanzavugaye, Kavimbi Chipusu, Hongyuan Huang, Yueqin Xu","doi":"10.3389/fphys.2025.1457197","DOIUrl":"10.3389/fphys.2025.1457197","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to enhance the efficiency and accuracy of thyroid nodule segmentation in ultrasound images, ultimately improving nodule detection and diagnosis. For clinical deployment on mobile and embedded devices, DeepLabV3+ strives to achieve a balance between a lightweight architecture and high segmentation accuracy.</p><p><strong>Methodology: </strong>A comprehensive dataset of ultrasound images was meticulously curated using a high-resolution ultrasound imaging device. Data acquisition adhered to standardized protocols to ensure high-quality imaging. Preprocessing steps, including noise reduction and contrast optimization, were applied to enhance image clarity. Expert radiologists provided ground truth labels through meticulous annotation. To improve segmentation performance, we integrated MobileNetV2 and Depthwise Separable Dilated Convolution into the Atrous Spatial Pyramid Pooling (ASPP) module, incorporating the Pyramid Pooling Module (PPM) and attention mechanisms. To mitigate classification imbalances, we employed Tversky loss functions in the ultrasound image classification process.</p><p><strong>Results: </strong>In semantic image segmentation, DeepLabV3+ achieved an impressive Intersection over Union (IoU) of 94.37%, while utilizing only 12.4 MB of parameters, including weights and biases. This remarkable accuracy demonstrates the effectiveness of our approach. A high IoU value in medical imaging analysis reflects the model's ability to accurately delineate object boundaries.</p><p><strong>Conclusion: </strong>DeepLabV3+ represents a significant advancement in thyroid nodule segmentation, particularly for thyroid cancer screening and diagnosis. The obtained segmentation results suggest promising directions for future research, especially in the early detection of thyroid nodules. Deploying this algorithm on mobile devices offers a practical solution for early diagnosis and is likely to improve patient outcomes.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1457197"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of performing mental exertion during cycling endurance exercise on fatigue indices: sex dependent differences.","authors":"Hamid Amoozi, Hamidreza Barzegarpoor, Hamid Rajabi, Duane C Button, Rana Fayazmilani","doi":"10.3389/fphys.2025.1522626","DOIUrl":"10.3389/fphys.2025.1522626","url":null,"abstract":"<p><strong>Introduction: </strong>Men and women have different performance abilities, where women have greater tolerance for fatigue in long-distance exercise. Part of this greater tolerance may be due, in part, differences in men's and women's mental fatigue capacity during exercise. Thus, the aim of this study was to examine the effect of cycling endurance exercise, along with mental fatigue, on the sex dependent differences in exercise tolerance.</p><p><strong>Methods: </strong>Twenty-five (15 women and 10 men) cyclists in a randomized, controlled, and crossover protocol performed three experimental sessions. In the first session, the cycling peak power output (PPO) was determined and 65% of PPO was used for intensity of the experimental sessions. In sessions 2 and 3, participants performed Cycling + Mental Exertion (ME) (cycling endurance exercise with a ME-stroop task) and Cycling + Movie (cycling endurance exercise while watching a movie). Serum cortisol concentration and a psychomotor vigilance task (PVT) were measured pre- and post-sessions. During the experimental sessions rate of perceived exertion (RPE) and heart rate (HR) were recorded every 10 min and participants completed the NASA-TLX questionnaire directly following the post- PVT.</p><p><strong>Results: </strong>Performing Cycling + ME was associated with a longer time to exhaustion (p < 0.05) and higher RPE following 40-70 min in women than men (p < 0.05). Cycling + ME increased HR following 40-70 min in women (p < 0.05). For both men and women cortisol concentration level was higher pre- to post-Cycling + ME with no difference between sexes. Women exhibited faster reaction times compared to men in both pre- and post-sessions.</p><p><strong>Discussion: </strong>Performing mental exertion with cycling endurance exercise impairs endurance performance. While our findings align with some previous research, we suggest that men may be more prone to mental fatigue; however, further research needed to confirm this.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1522626"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer's disease.","authors":"Chenyu Zhuang, Hengyu Yan, Jiayu Lu, Yifan Zhou, Yanqing Liu, Guoshan Shi, Yan Li","doi":"10.3389/fphys.2025.1529981","DOIUrl":"10.3389/fphys.2025.1529981","url":null,"abstract":"<p><strong>Background: </strong>Amyloid-β protein (Aβ) accumulation is a defining characteristic of Alzheimer's disease (AD), resulting in neurodegeneration and a decline in cognitive function. Given orexin's well-documented role in enhancing memory and cognition, this study investigates its potential to regulate Aβ-induced neurotoxicity, offering new perspectives into AD management.</p><p><strong>Methods: </strong>This paper simulated Aβ accumulation in the hippocampus of AD patients by administering Aβ_1-42 oligomers into the bilateral hippocampal dentate gyrus of ICR mice. Inflammatory cytokines (IL-6, TNF-α) and orexin-A levels were measured by ELISA. Additionally, the excitability of orexinergic neurons was assessed by IHC targeting c-Fos expression. These methodologies evaluated the Aβ-induced neuroinflammation, orexinergic system functionality, and dexamethasone's (Dex) effects on these processes.</p><p><strong>Results: </strong>Injection of Aβ_1-42 oligomer resulted in elevated levels of IL-6, TNF-α, and orexin-A in the hippocampus, as well as increased excitability of orexinergic neurons in the lateral hypothalamus (LH). Dex treatment reduced neuroinflammation, causing a reduction in orexin-A levels and the excitability of orexinergic neurons.</p><p><strong>Conclusion: </strong>Aβ-induced neuroinflammation is accompanied by enhanced levels of orexin-A and orexinergic neuron excitability. These findings suggest that the enhanced functionality of the orexinergic system may become a compensatory neuroprotective mechanism to counteract neuroinflammation and enhance cognitive function.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1529981"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}