Neurochemistry international最新文献

{"title":"Schwann cells as a therapeutic target for amyotrophic lateral sclerosis: A TDP-43 focussed review","authors":"Katherine N. Lewis ,&nbsp;David G. Gonsalvez ,&nbsp;Bradley J. Turner ,&nbsp;Samantha K. Barton","doi":"10.1016/j.neuint.2025.106055","DOIUrl":"10.1016/j.neuint.2025.106055","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is an incurable, lethal neurodegenerative disease and a proteinopathy with &gt;97 % of cases characterised by pathological accumulation of TDP-43. TDP-43 is ubiquitously expressed and its pathological accumulation has now been identified in non-neuronal cells in both the central and peripheral nervous systems. Thus, the expansion to exploring other cells and their contribution to ALS pathogenesis may be the key to finding more effective treatments. Schwann cells are the myelinating cells of the peripheral nervous system, that encase neuronal axons to propagate action potentials, maintain neuronal health, and respond to neuronal activity in the extracellular environment. Despite Schwann cells being identified to exhibit aberrant TDP-43 proteinopathy in ALS patients, their role in disease remains elusive. Here, we review the potential contributions of Schwann cells to ALS as well as the prospective benefits of harnessing Schwann cells treat the disease.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106055"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two phosphomimetic sites in the GABA transporter GAT1 C-terminus selectively regulate transporter interactions with distinct types of PDZ domains in vitro","authors":"Iveta Koščová,&nbsp;Martina Baliova,&nbsp;Frantisek Jursky","doi":"10.1016/j.neuint.2025.106058","DOIUrl":"10.1016/j.neuint.2025.106058","url":null,"abstract":"<div><div>The GABA transporter GAT1 is a membrane protein that participates in GABA signalling in the brain and certain peripheral tissues. GAT1 contains a C-terminal PDZ motif (-A⁵⁹⁷Y⁵⁹⁸I⁵⁹⁹), previously classified as a type II (ΦXΦ) motif, where PDZ interaction should depend on non-phosphorylatable hydrophobic (Φ) residues at PDZ positions 0 (I⁵⁹⁹) and −2 (A⁵⁹⁷). We recently found that a GAT1 C-terminal peptide unconventionally binds to the PDZ1 domain of syntenin-1 and to the PDZ2 domain of PSD95 by using different PDZ interaction schemes, specifically 0,-1 and 0,-3, respectively. In this work, we used phosphomimetic amino acid mutagenesis to investigate the role of phosphorylatable amino acids in the GAT1 C-terminus in binding to these two domains. The mutagenesis and molecular docking experiments suggested that phosphorylation of tyrosine 598 at PDZ position −1 might affect the interaction with the PDZ1 domain of syntenin-1, but it did not affect the interaction with the PDZ2 domain of PSD95. On the other hand, a phosphomimetic but not a neutral mutation of the remote serine residues 592 and 594 at PDZ positions −7 and −5, respectively, affected the interaction of the GAT1 PDZ motif with the PDZ2 domain of PSD95, but not with the PDZ1 domain of syntenin-1. These findings suggest the existence of at least two domain-specific GAT1 PDZ interaction modes regulated by two distinct potentially phosphorylatable serine and tyrosine residues in the GAT1 C-terminus.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106058"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese stimulates ferroptosis to trigger neurotoxicity in mice and HT22 cells: the role of NCOA4-mediated ferritinophagy","authors":"Zehua Tao ,&nbsp;Xinyu Zhang ,&nbsp;Jian Chen ,&nbsp;Jing Hu ,&nbsp;Suhua Wang ,&nbsp;Guangwei Xing ,&nbsp;Ngwa Adeline Ngeng ,&nbsp;Abdul Malik ,&nbsp;Kwaku Appiah-Kubi ,&nbsp;Marcelo Farina ,&nbsp;Anatoly V. Skalny ,&nbsp;Alexey A. Tinkov ,&nbsp;Michael Aschner ,&nbsp;Bobo Yang ,&nbsp;Rongzhu Lu","doi":"10.1016/j.neuint.2025.106065","DOIUrl":"10.1016/j.neuint.2025.106065","url":null,"abstract":"<div><div>Manganese (Mn), an essential trace element for physiological functions, can induce neurotoxicity through iron-dependent oxidative stress mechanisms when present in excess. This study reveals that Mn triggers ferroptosis in neural cells via nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Using <em>in vivo</em> (Mn-exposed mice) and <em>in vitro</em> (hippocampal HT22 cells) models, we demonstrated that Mn exposure disrupts iron homeostasis, elevating brain iron accumulation and downregulating ferroptosis-protective proteins (SLC7A11 and GPX4). The ferroptosis inhibitor ferrostatin-1 effectively counteracted Mn-induced cell death, whereas the extracellular iron chelator deferoxamine showed limited protection. Crucially, NCOA4 knockdown significantly mitigated Mn-induced iron overload and cell viability loss, outperforming deferoxamine. These findings establish ferritinophagy as a central mechanism in Mn neurotoxicity and highlight the therapeutic potential of targeting intracellular iron regulation over extracellular chelation. Our work provides a mechanistic foundation for developing interventions against Mn-associated neurodegenerative disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106065"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine","authors":"Faheem Shehjar,&nbsp;Reetika Mahajan,&nbsp;Shayaan Shahnaz,&nbsp;Zahoor A. Shah","doi":"10.1016/j.neuint.2025.106059","DOIUrl":"10.1016/j.neuint.2025.106059","url":null,"abstract":"<div><div>Stroke remains a leading cause of death and disability, driven by complex interactions among genetic, epigenetic, and environmental factors. Advances in genomic technologies have elucidated the role of common polygenic variants and rare monogenic mutations in determining susceptibility to stroke subtypes. Genome-wide association studies have identified key loci, including <em>Histone Deacetylase 9</em> (HDAC9), <em>Paired-like Homeodomain Transcription Factor 2</em> (PITX2), <em>Zinc Finger Homeobox 3</em> (ZFHX3), and <em>Collagen Type IV Alpha 1 Chain</em> (COL4A1), associated with vascular inflammation, atrial fibrillation, and small vessel dysfunction. Monogenic disorders such as <em>Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy</em> (CADASIL; <em>NOTCH3</em>), Fabry disease (<em>GLA</em>), and Sickle Cell Disease (SCD; <em>HBB</em>) illustrate the impact of single-gene mutations on early-onset or familial stroke. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) regulate pathways related to apoptosis, inflammation, angiogenesis, and blood-brain barrier dysfunction. Pharmacogenomic profiling, involving genes such as <em>CYP2C19</em>, <em>VKORC1</em>, and <em>SLCO1B1</em>, can guide individualized therapy with antiplatelets, anticoagulants, and statins. Collectively, these advances are steering stroke care toward precision medicine, integrating multi-omics data and gene-targeted strategies for improved prevention, diagnosis, and treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106059"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic interaction of oligodendrocyte precursor cells with other cell types in the central nervous system","authors":"Jiali Li ,&nbsp;Shangyao Qin ,&nbsp;Hong Liu ,&nbsp;Ziwei Dai ,&nbsp;Zhida Lan ,&nbsp;Yimin Yuan ,&nbsp;Zhida Su","doi":"10.1016/j.neuint.2025.106050","DOIUrl":"10.1016/j.neuint.2025.106050","url":null,"abstract":"<div><div>Traditionally, oligodendrocyte precursor cells (OPCs) were primarily regarded for their differentiation potential to mature oligodendrocytes that ensheath central nervous system (CNS) axons through myelin formation. Recent breakthroughs in single-cell sequencing and <em>in vivo</em> imaging technologies have revolutionized our understanding, revealing that OPCs engage in extensive dynamic interactions with diverse CNS cell populations during neurodevelopment, tissue homeostasis maintenance, and pathological microenvironment remodeling. Notably, while OPCs exhibit relatively conserved phenotypic signatures, their functional plasticity within heterogeneous microenvironments demonstrates significant spatial specificity and disease-context dependence. In this review, we will systematically sort out the molecular interaction mechanism between OPCs and neurons, astrocytes, microglia, and vascular endothelial cells, deeply analyze their dynamic functional profiles, and focus on discussing: (1) the fine-tuning regulatory model of neuronal circuits mediated by OPCs at the developmental stage (2) the bidirectional regulatory mechanism of OPCs involved in maintaining the metabolic-immune balance under homeostasis; (3) OPC functional reprogramming in the pathological process of multiple sclerosis, cerebral ischemia, etc. This review aims to consolidate current evidence into a cohesive perspective on OPC multimodal functions, evaluate non-myelinating contributions, and discuss promising therapeutic targets for neural regenerative medicine.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106050"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic exercise rescues synaptic plasticity in early-stage Alzheimer's disease by suppressing miR-3473e to activate EphB2-dependent NMDA/AMPA receptor signaling","authors":"Xiangli Tong ,&nbsp;Zhen Tong ,&nbsp;Weijia Wu ,&nbsp;Jialun Yang ,&nbsp;Juan Wang ,&nbsp;Yang Wang ,&nbsp;Dandan Chen ,&nbsp;Yiyang Wang ,&nbsp;Fanqi Zeng ,&nbsp;Qiyan Du ,&nbsp;Yishan Chen ,&nbsp;Wenfeng Liu","doi":"10.1016/j.neuint.2025.106023","DOIUrl":"10.1016/j.neuint.2025.106023","url":null,"abstract":"<div><div>Cognitive dysfunction in early-stage Alzheimer's disease (AD) involves significant impairments in synaptic plasticity and dendritic spines integrity. Intriguingly, exercise interventions have demonstrated efficacy in enhancing cognitive function. However, the precise molecular mechanisms, particularly the upstream endogenous regulators (such as miRNAs) through which exercise mediates this synaptic improvement, remain unclear. Our findings indicated that 12 weeks of aerobic exercise effectively increased learning and memory, promoted amyloid beta (Aβ) and cerebral amyloid angiopathy (CAA) clearance in early-stage AD. Furthermore, aerobic exercise markedly enhanced dendritic spines density of pyramidal neurons in cortical layers II/III and the hippocampal CA1 region, as well as the expression of synapse-associated proteins such as cAMP response element-binding protein (CREB), synaptophysin (SYN), and postsynaptic density protein 95 (PSD95). Whole genome RNA sequencing (RNA-Seq) and bioinformatics analysis was performed to identify miR-3473e, a target closely related to AD and also a response factor that serves as a key mediator of aerobic exercise benefits. Subsequent findings revealed that miR-3473e was overexpressed in the brains of APP/PS1 mice, whereas aerobic exercise led to a decrease in its expression. Moreover, aerobic exercise enhanced its downstream targets, EPH receptor B2 (EphB2) and solute carrier family 1 member 1 gene (Slc1a1) as well as increased downstream GluN1, GRIA1 and <em>p</em>-GluN2B/GluN2B protein expression levels. In summary, we demonstrate that aerobic exercise can improve synaptic plasticity, and these effects are mediated via suppression of miR-3473e and regulation EphB2-NMDA/AMPA receptor signaling pathway, underscoring the potential of aerobic exercise to enhance cognitive function in early-stage of AD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"189 ","pages":"Article 106023"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DUSP1-mediated suppression of p38 MAPK signaling pathway reduces ferroptosis in cerebral ischemia-reperfusion injury.","authors":"Shuyin Ma, Xiaodong Zhang, Jiaxin Fan, Mengying Chen, Qingling Yao, Nan Zhang, Kaili Shi, Minyu Duan, Han Yang, Tiantian Gao, Xiaodong Ma, Jingyi Wang, Weina Li, Chuxiao Zhou, Shuqin Zhan","doi":"10.1016/j.neuint.2025.106024","DOIUrl":"10.1016/j.neuint.2025.106024","url":null,"abstract":"<p><p>Ferroptosis constitutes a critical pathological mechanism in cerebral ischemia-reperfusion injury (CI/RI), significantly influencing neurological outcomes. While dual specificity phosphatase 1 (DUSP1) demonstrates neuroprotective effects against CI/RI, its regulatory role in ferroptosis remains to be elucidated. This study systematically investigated the therapeutic potential of DUSP1 through ferroptosis modulation in both in vitro and in vivo models. Using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated PC12 cells with either DUSP1 overexpression or knockdown, we comprehensively assessed ferroptosis parameters including cell viability, malondialdehyde content, glutathione levels, intracellular iron concentration, reactive oxygen species accumulation, and expression of key ferroptosis-related proteins. In middle cerebral artery occlusion/reperfusion (MCAO/R) rat models, pharmacological inhibition of DUSP1 was employed to evaluate its impact on cerebral infarction volume, neurological deficits, histopathological changes, and ferroptosis biomarkers. Mechanistic studies incorporated the p38 mitogen-activated protein kinase pathway inhibitor adezmapimod. Our results demonstrated that (1) ferroptosis was significantly induced in both the OGD/R and MCAO/R models, accompanied by upregulated DUSP1 expression; (2) DUSP1 overexpression attenuated ferroptosis and ameliorated CI/RI, whereas genetic knockdown exacerbated these pathological processes; (3) pharmacological inhibition of DUSP1 aggravated cerebral injury and ferroptosis markers in MCAO/R rats; and (4) adezmapimod treatment effectively rescued ferroptosis progression in DUSP1-deficient cells by restoring glutathione peroxidase 4 and ferroportin expression while downregulating transferrin receptor and Ferritin Heavy Chain levels. These findings establish that DUSP1 confers neuroprotection against CI/RI through p38-mediated ferroptosis regulation, suggesting its promise as a novel therapeutic target for ischemic stroke.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106024"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Casticin inhibits the release of synaptic vesicular glutamate from rat hippocampal nerve terminals","authors":"Cheng-Wei Lu ,&nbsp;Tzu-Yu Lin ,&nbsp;Wun-Jing Pan ,&nbsp;Ya-Ying Chang ,&nbsp;Kuan-Ming Chiu ,&nbsp;Ming-Yi Lee ,&nbsp;Su-Jane Wang","doi":"10.1016/j.neuint.2025.106025","DOIUrl":"10.1016/j.neuint.2025.106025","url":null,"abstract":"<div><div>The effect of casticin, major polymethoxyflavone extracted from <em>Vitex rotundifolia</em>, on glutamate release and its underlying mechanisms was investigated in rat hippocampal synaptosomes. Casticin inhibited 4-aminopyridine (4-AP)-evoked glutamate release, with an IC₅₀ of approximately 7.2 μM. It reduced the 4-AP-evoked increase in intrasynaptosomal Ca²⁺ concentration without affecting the synaptosomal membrane potential. The inhibitory effect of casticin on glutamate release was markedly prevented by ω-conotoxin GVIA, an N-type Ca²⁺ channel blocker, but not by ω-agatoxin VIA, a P/Q-type Ca²⁺ channel blocker. Further analysis of FM1-43 dye release showed that casticin suppressed glutamate release by decreasing synaptic vesicle exocytosis. Consistently, casticin also reduced 4-AP-induced phosphorylation of synapsin I, a presynaptic protein that regulates synaptic vesicle mobilization. Transmission electron microscopy (TEM) revealed that casticin decreased the proportion of release-competent synaptic vesicles in 4-AP-stimulated hippocampal synaptosomes. Taken together, these findings suggest that casticin inhibits glutamate release from rat hippocampal nerve terminals, potentially by suppression of N-type Ca²⁺ channel and reducing the availability of synaptic vesicles for exocytosis.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"189 ","pages":"Article 106025"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic dysregulation and the etiology of spina bifida","authors":"Tabitha Lumour-Mensah ,&nbsp;Susan Korrick ,&nbsp;Bernardo Lemos ,&nbsp;Maitreyi Mazumdar","doi":"10.1016/j.neuint.2025.106033","DOIUrl":"10.1016/j.neuint.2025.106033","url":null,"abstract":"<div><div>Spina bifida is a complex and multifactorial congenital defect driven by both genetic and environmental factors. As such, epigenetic studies of spina bifida present an opportunity to study the joint contribution of both genes and the environment in the development of this disorder. This review focuses specifically on epigenetic research that may help us to understand the ways in which dysregulation of the epigenome and downstream cellular processes can confer increased risk of spina bifida. To do so, we discuss the epigenetic regulation of genes linked to spina bifida risk among children born with the disorder and their parents as well as evidence from experimental studies. We also discuss pathways necessary for normal neural tube development and specific documented dysregulation of these pathways in individuals with spina bifida. We conclude that the epigenome plays an important role in spina bifida etiology and should be further studied in additional populations, and tissue types, as well as cellular and animal models.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"189 ","pages":"Article 106033"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating metabolomic changes in Lennox-Gastaut syndrome: correlation with clinico-radiological severity","authors":"Jayantee Kalita ,&nbsp;Aditi Pandey ,&nbsp;Firoz M. Nizami ,&nbsp;Ashish K. Dubey ,&nbsp;Bikash Baishya","doi":"10.1016/j.neuint.2025.106032","DOIUrl":"10.1016/j.neuint.2025.106032","url":null,"abstract":"<div><div>Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by multiple types of seizures typically occurring between 1 and 7 years of age, cognitive impairment and characteristic electroencephalographic abnormalities. Circulating metabolomic profile may give insight into the ongoing metabolic pathway abnormalities in these patients, but there is no such study. We report NMR based metabolomic profile in LGS and its association with clinical severity, MRI changes and EEG findings. LGS children between 2 and 18 years were included based on clinical and EEG diagnostic criteria. Detailed neurological examinations, frequency and type of seizures, EEG changes, cranial MRI and NMR based serum metabolomic profile were measured. The Clinical Global Impairment Severity Scale (CGI-S) was used to rate severity of LGS. Twenty-six LGS patients and 11 healthy matched controls were included. The median age of the patients was 6 (range 2–17) years, and 19 were males. Their median CGI-S score was 6, and all had more than one type of seizures. Seven metabolites namely lactate, glucose, glutamate, pyruvate, glutamine, glycine, citrate and creatinine were crucial for discrimination of LGS from the controls, among which glutamate was upregulated and citrate, pyruvate, and glutamine were down regulated in LGS. Glutamate associated with developmental quotient (r = −0.48) and pyruvate with focal seizures (r = 0.47) and cystic encephalomalacia on cranial MRI (p = 0.02). NMR metabolomic profile including glutamate, glutamine, glycine, glucose, pyruvate, lactate, citrate and creatinine can discriminate LGS from the controls. Role of antiglutamatergic drugs may be beneficial in controlling seizures, and needs future study.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"189 ","pages":"Article 106032"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}