Experimental Biology and Medicine最新文献

{"title":"N-acetyl-L-cysteine improves mitochondrial and oxidative defects in the acadian variant of fanconi syndrome.","authors":"Inas Al-Younis, Rebeca Martín-Jiménez, Mehtab Khan, Yann Baussan, Caroline Jose, Yves Thibeault, Etienne Hebert-Chatelain","doi":"10.3389/ebm.2025.10448","DOIUrl":"10.3389/ebm.2025.10448","url":null,"abstract":"<p><p>The Acadian variant of Fanconi Syndrome (AVFS) is a rare genetic disorder characterized by renal deficiencies. AVFS is caused by a mutation to <i>NDUFAF6</i> encoding a complex I assembly factor, and leading to metabolic alterations. We confirmed that fibroblasts derived from AVFS patients have lower complex I activity, mitochondrial membrane potential and cellular respiration. These mitochondrial defects were accompanied by higher levels of 8-hydroxy-2'deoxyguanosine, malondialdehyde and carbonyl, which are markers of oxidative damage to DNA, lipids and proteins, respectively. Thus, we hypothesized that the antioxidant N-Acetyl-L-cysteine (NAC) would reduce oxidative stress and mitochondrial defects in AVFS fibroblasts. Treatment with NAC during 5 days partially restored complex I activity, mitochondrial membrane potential and cellular respiration in AVFS fibroblasts. NAC also prevented oxidative damage in AVFS fibroblasts. This work shows for the first time that the physiopathology of AVFS includes high oxidative stress. It also reveals that NAC and other antioxidant-based strategies might represent an effective pharmacological treatment for AVFS.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10448"},"PeriodicalIF":2.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247184","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":"Diagnostic accuracy of <i>Pf</i>HRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance.","authors":"Sharley A Wasena, Clinton O Onyango, Shamim W Osata, Samuel B Anyona, Evans Raballah, Ivy Hurwitz, Philip D Seidenberg, Collins Ouma, Qiuying Cheng, Kristan A Schneider, Douglas J Perkins","doi":"10.3389/ebm.2025.10585","DOIUrl":"10.3389/ebm.2025.10585","url":null,"abstract":"<p><p>Malaria remains a significant cause of childhood morbidity and mortality, with <i>Plasmodium falciparum</i> Histidine-Rich Protein 2 (<i>Pf</i>HRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, persistent <i>Pf</i>HRP2 antigenemia and gene deletions can cause false-positive and false-negative results, compromising their accuracy for malaria case management and surveillance. This study evaluated the diagnostic performance and antigen persistence of <i>Pf</i>HRP2-mRDTs using data from a longitudinal birth cohort of 750 children followed monthly from birth to 36 months in a holoendemic region of Kenya. Malaria diagnosis was performed using both microscopy and mRDTs, with a total of 15,006 clinical events recorded from 573 children between 2017 and 2023. Data from an independent acute febrile cohort of 937 children (<5 years) followed for 14 days was analyzed to validate the findings. The mRDT showed a high sensitivity of 97.27% but a moderate specificity of 65.00% in acute febrile illness, indicating frequent false-positive results. The positive predictive value was low (35.10%), suggesting that confirmatory testing is needed, while the negative predictive value was high (98.89%), reinforcing the reliability of mRDTs in ruling out malaria. Persistent <i>Pf</i>HRP2 antigenemia was observed, with a median antigen clearance time of 51.14 days, respectively. Higher initial parasite densities (>50,000/μL) were associated with a slower antigen decay rate (<i>p</i> = 0.001), highlighting the challenge of interpreting positive mRDT results after treatment. Validation using the acute febrile cohort showed that mRDT specificity exceeded 95% at initial diagnosis and follow-up. Overall, <i>Pf</i>HRP2-based mRDTs remain valuable for frontline malaria diagnosis but are limited by antigen persistence, leading to false positives in follow-up testing. Where feasible, integration of confirmatory diagnostic methods, such as microscopy or molecular assays, could improve the performance of malaria case management and clinical decision making, particularly in high-transmission settings.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10585"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233624","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":"A double-edged effect of hypoxia on astrocyte-derived exosome releases.","authors":"Yang Jie Tseng, Hui-Ju Huang, Chien-Hui Lin, Anya Maan-Yuh Lin","doi":"10.3389/ebm.2025.10559","DOIUrl":"10.3389/ebm.2025.10559","url":null,"abstract":"<p><p>Exosomes are the smallest extracellular vesicles secreted from cells, carrying different cargos, including nucleic acids, proteins and others which transfer from cells to cells. The properties of exosomes depend on the donor cells. Hypoxia, referring to a sublethal and insufficient oxygen supply, reportedly influences exosome secretion of hypoxic cells. In the present study, we focused on the effects of hypoxia on exosomes obtained from CTX-TNA2 astrocyte cells exposed to different durations of hypoxia followed by normoxia as a model of hypoxic preconditioning. To evaluate the functions of exosomes, primary cultured cortical neurons were treated with hemin, a potent neurotoxin. Our sulforhodamine B assay showed that incubation of hemin (30 μM) consistently induced neuronal death. Co-incubation of exosomes from CTX-TNA2 cells subjected to 2 hr-hypoxia plus 6 hr-renormoxia (2H/6R exosomes), but not 12 hr-hypoxia plus 24 hr-renormoxia (12H/24R exosomes), attenuated hemin-induced cell death and reduction in growth associated protein 43 level (a biomarker of neurite outgrowth). Western blot assay demonstrated that 2H/6R exosomes attenuated hemin-induced elevations in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1). In contrast, 12H/24R exosomes did not alter hemin-induced elevation in HO-1 but further augmented hemin-induced increases in iNOS and COX-2. Moreover, 2H/6R exosomes attenuated hemin-induced reduction in glutathione hydroperoxidase 4 (a biomarker of ferroptosis) and elevation in active caspase 3 (a biomarker of apoptosis) while 12H/24R exosomes did not effectively alter hemin-induced programed cell death. In conclusion, our study showed that 2H/6R exosomes possessed neuroprotective activities while 12H/24R exosomes had mild pro-inflammatory activities, suggesting that different hypoxic preconditionings influenced CTX-TNA2 cells which then secreted exosomes with differential biological activities. These findings highlight a double-edged role of hypoxia on exosome functions.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10559"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224869","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":"Optimal transport reveals immune perturbation and fingerprints over time in COVID-19 vaccination.","authors":"Zexuan Wang, Jiong Chen, Matei Ionita, Qipeng Zhan, Zhuoping Zhou, Li Shen","doi":"10.3389/ebm.2025.10445","DOIUrl":"10.3389/ebm.2025.10445","url":null,"abstract":"<p><p>Mass cytometry enables high-throughput characterization of heterogeneous cell populations at single-cell resolution, using metal isotopes to capture cellular signals and avoiding the spectral overlap common in flow cytometry. Despite advancements, conventional data analysis often focuses on manual gating or clustering within specific samples, overlooking disparities across subjects or biological samples. To address this gap, we propose a novel framework that treats the cell-by-protein matrix as a high-dimensional distribution, using Quantized Optimal Transport (QOT) to quantify distances between samples based on their cellular protein expression profiles. This approach allows for a direct comparison of distributions without relying on predefined gating strategies, capturing subtle variations in the data. We validated our method through two experiments using real-world time-series Coronavirus Disease 2019 (COVID-19) cytometry data. First, we conducted a leave-one-out analysis to identify immunologically unstable proteins over time, revealing CD3 and CD45 as the proteins changing the most during the vaccine response. Second, we aimed to capture individual immune fingerprints over time by calculating pairwise Wasserstein distances between samples and applying hierarchical clustering. Using silhouette scores to evaluate clustering effectiveness, we identified optimal combinations of immunological markers that effectively grouped samples from the same participant across different time points. Our findings demonstrate that the QOT framework provides a robust and flexible tool for cohort-level analysis of mass cytometry data, enabling the identification of unstable immunological markers and capturing immune response heterogeneity among vaccinated cohorts.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10445"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224871","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":"Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring.","authors":"Chandra Mohan Reddy Muthumula, Yaswanthi Yanamadala, Kuppan Gokulan, Kumari Karn, Helen Cunny, Vicki Sutherland, Janine H Santos, Sangeeta Khare","doi":"10.3389/ebm.2025.10468","DOIUrl":"10.3389/ebm.2025.10468","url":null,"abstract":"<p><p>Despite the highly effective impact of antiretroviral therapy (ART) in reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implications of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight into the potential effect of <i>in utero</i> and lactational exposure to ART on gut microbiota populations and short-chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline in <i>Firmicutes</i> in males, and an increase in <i>Actinobacteria</i> among males and females. Furthermore, a sex-specific distribution reorganization of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Akkermansia</i> was identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10468"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224870","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":"Chronic administration of a cannabis-derived mixture at an antihyperalgesic dose does not significantly enhance hepatotoxicity or the development of metabolic dysfunction-associated steatohepatitis in male mice.","authors":"Kim B Pedersen, Tomislav Jelesijevic, Tamara M Morris, Sarah M Melton, Ashley S Henderson, John F Glenn, Gregory J Davenport, Martin J J Ronis, Peter J Winsauer","doi":"10.3389/ebm.2025.10356","DOIUrl":"10.3389/ebm.2025.10356","url":null,"abstract":"<p><p>Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic pathology following chronic administration of a cannabinoid mixture (NEPE14) at a dose equivalent to one previously demonstrating antihyperalgesic effects in rats. The effects of NEPE14 were investigated in a mouse model of MASH produced by feeding a Western diet rich in fat and simple sugars. After 24 weeks of NEPE14 administration, there was no hepatotoxicity in mice receiving the control diet and no significant exacerbation of MASH in mice receiving the Western diet. In conclusion, no chronic liver toxicity was observed, but there was also no evidence for protection against MASH by this product.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10356"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208117","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":"Anesthesia-induced developmental neurotoxicity in the setting of systemic inflammation: the role of microglia.","authors":"Nemanja Useinovic, Adre Newson, Michelle Near, Stefan Maksimovic, Benjamin Volvovitz, Nidia Quillinan, Vesna Jevtovic-Todorovic","doi":"10.3389/ebm.2025.10549","DOIUrl":"10.3389/ebm.2025.10549","url":null,"abstract":"<p><p>Although it is well documented in animal research that an early exposure to general anesthetics during critical stages of synaptogenesis disturbs normal brain development ultimately leading to cognitive and affective impairments, it is less clear whether and how surgical interventions and/or underlying systemic inflammation impact the detrimental effects of general anesthetics. Some emerging evidence suggests that aseptic systemic inflammation preceding exposure to the commonly used general anesthetics worsens anesthesia-induced neuroapoptosis and activates inflammasome pathways while resulting in impaired cognitive-affective behaviors. To improve our understanding of the underlying mechanisms, here we focused on multicellular interactions between damaged neurons and microglia since microglia is the resident macrophages within the brain that respond to stress. Using infant rats (post-natal day 7) and most commonly used inhaled anesthetic, sevoflurane, we examine microglia role in sevoflurane-induced inflammation-propagated developmental neurotoxicity. We show that sevoflurane exposure leads to a significant neuroapoptosis in young rat pup hippocampal subiculum, a neuroapoptosis that is worsened in the setting of systemic inflammation caused by either lipopolysaccharide (LPS) injection or trauma (tibial fracture). The worsening is not only shown in terms of the intensity of neuroapoptosis but in its duration and onset. We further report that sevoflurane-induced neuroapoptosis triggers activation of microglia, which in turn releases proinflammatory cytokine MCP-1 and upregulates endothelial cell adhesion molecule, ICAM-1. This leads to T-lymphocyte infiltration in the hippocampal subiculum, an event that further perpetuates microglia activation in an attempt to control neuroapoptosis which is suggested by the fact that microglia depletion leads to a significant worsening of sevoflurane-induced developmental neuroapoptosis. Our work gets us a step closer to making our animal work more relevant to the clinical setting and hence more translational. This is vitally important considering that exposure to anesthesia is exceedingly rare in the absence of any kind of a pathological process.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10549"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198637","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":"<i>In vivo</i> silencing of the thalamic Ca_V3.1 voltage-gated calcium channels demonstrates their region-specific role in anesthetic mediated hypnosis.","authors":"Tamara Timic Stamenic, Simon Feseha, Brier Fine-Raquet, Vasilije P Tadic, Slobodan M Todorovic","doi":"10.3389/ebm.2025.10553","DOIUrl":"10.3389/ebm.2025.10553","url":null,"abstract":"<p><p>Although substantial progress has been made in the last three decades towards our understanding of how general anesthetics (GAs) act at the molecular level, much less is known about how GAs cause loss of consciousness at the level of neuronal networks. The role of thalamus as an important brain region in anesthetic-induced hypnosis is relatively well established, but the specific roles of voltage-gated ion channels in different functional regions of the thalamus in anesthetic mechanisms are not well studied. To address this gap in knowledge, we selectively silenced the <i>Cacna1g</i> gene that encodes the low-threshold-activated Ca_V3.1 T-type voltage-gated calcium channel subunit by injecting short-hairpin RNA (shRNA) into midline and intralaminar - nonspecific thalamus (MIT) and sensory - specific ventrobasal (VB) thalamic nuclei in wild-type (WT) mice. Control animals were injected with scrambled shRNA. To validate our silencing approach, we performed patch-clamp experiments in acute thalamic slices <i>ex vivo</i>. In injected animals we determined anesthetic endpoints such as hypnosis measured with loss of righting reflex (LORR) and immobilization measured with loss of withdrawal reflex (LOWR) <i>in vivo</i> after administration of a traditional volatile GA isoflurane. Effective Ca_V3.1 channel knock-down was documented by greatly diminished amplitudes of T-currents and absence of rebound burst firing in our patch-clamp recordings from thalamic slices. We found that knocking down Ca_V3.1 channels in MIT significantly decreased inhaled isoflurane concentration that is required to induce LORR, but it did not affect speed of anesthetic induction and the immobilizing effect of isoflurane. In contrast, knocking down the Ca_V3.1 channel in the VB thalamus did not affect any of the measured anesthetic endpoints. Hence, we concluded that Ca_V3.1 channels in nonspecific MIT thalamus have a preferential role in anesthetic hypnosis when compared to the sensory VB thalamus.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10553"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198636","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":"Involvement of EGFR-AKT signaling in hemin-induced neurotoxicity.","authors":"Hui-Ju Huang, Yang-Jie Tseng, I-Jung Lee, Yu-Li Lo, Anya Maan-Yuh Lin","doi":"10.3389/ebm.2025.10554","DOIUrl":"10.3389/ebm.2025.10554","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH), as bleeding from ruptured vessels within the brain, is the second leading neuropathological problem following ischemic stroke. In the present study, the involvement of epithelial growth factor receptor (EGFR)-tyrosine kinase (TK) signaling underlying ICH-related neurodegeneration was investigated using afatinib, a clinically available EGFR-tyrosine kinase inhibitor (EGFR-TKI). We employed hemin (a breakdown product of hemoglobin) to mimic the pathophysiology of ICH in primary cultured cortical neurons. Using a lactate dehydrogenase (LDH) assay, incubation of hemin concentration- and time-dependently induced neuronal death. Simultaneous incubation of afatinib (10 nM) significantly inhibited hemin (30 μM)-induced neuronal death. Immunofluorescent data demonstrated that co-treatment of afatinib for 1 h attenuated hemin (30 μM)-induced elevation in phosphorylated-EGFR (p-EGFR) immunoreactivity and neurite impairment. Western blot assay demonstrated that co-incubation of afatinib for 16 h diminished hemin-induced elevation in p-EGFR and p-AKT, tumor necrosis factor-α and cyclooxygenase 2 (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1, an enzyme catalyzing heme/hemin), glutathione hydroperoxidase 4 and receptor-interacting protein 3 (two biomarkers of ferroptosis and necroptosis). In addition, co-treatment of afatinib for 24 h inhibited hemin-induced NO production in the culture medium. In conclusion, our study shows that afatinib via blocking EGFR-AKT signaling inhibits hemin-induced EGFR-AKT activation, neuroinflammation, HO-1 expression and programed cell death, suggesting that EGFR-AKT signaling is involved in hemin-induced neurotoxicity and may be a druggable target for ICH.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10554"},"PeriodicalIF":2.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180969","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":"α-linolenic acid-induced facilitation of GABAergic synaptic transmission is mediated via acid-sensing ion channel (ASIC1a) activity in the basolateral amygdala.","authors":"Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga, Ann M Marini","doi":"10.3389/ebm.2025.10545","DOIUrl":"10.3389/ebm.2025.10545","url":null,"abstract":"<p><p>Epilepsy affects more than 70 million people worldwide. A seizure focus that develops in different cortical brain regions can present as either focal or generalized seizures. Temporal lobe epilepsy is a highly pharmacoresistant form of epilepsy that involves the amygdala, hippocampus with or without hippocampal sclerosis as well as other limbic structures. Loss and/or dysfunction of GABAergic inhibitory neurons play a critical role in tipping the balance toward excitation. Synchronous burst firing is a feature of inhibitory neurons that is thought to regulate and rectify large excitatory neuronal networks in the BLA and is thought to underlie higher cognitive function. Acid sensing ion channels (ASIC) activated by decreases in pH, the presence of ammonium ion or a slight lowering of temperature are present on excitatory and inhibitory neurons and can alter excitability. The net effect of the activation of ASIC1a channels in the BLA is inhibition. ASIC1a channels are active in the basal state, enhancing primarily GABAergic inhibition by direct depolarization of interneurons but also by indirect excitation of interneurons via ASIC1a-mediated depolarization of pyramidal neurons. In this study, we examine the contribution of ASIC1a channel activation on alpha-linolenic acid (ALA)-induced GABAergic inhibitory synchronous burst firing in the BLA. Our results show that ALA initiates inhibitory bursts that are dependent, in part, on the activation of ASIC1a channels that may in turn be mediated by mature brain-derived neurotrophic factor.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10545"},"PeriodicalIF":2.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180912","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}