Journal of Molecular Neuroscience最新文献

{"title":"Comprehensive in Silico Reclassification of MECP2 Variants of Uncertain Significance in Rett Syndrome: Performance Evaluation and Structural Analysis","authors":"Sertaç Atalay,&nbsp;Özlem Yalçın Çapan","doi":"10.1007/s12031-025-02421-9","DOIUrl":"10.1007/s12031-025-02421-9","url":null,"abstract":"<div><p>Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by missense variants in the <i>MECP2</i> gene. However, the presence of variants of uncertain significance (VUS) poses major challenges for clinical diagnosis and genetic counseling. In this study, we systematically evaluated the performance of 33 in silico prediction tools using a curated ClinVar dataset of <i>MECP2</i> missense variants. Performance metrics included accuracy, sensitivity, specificity, area under the curve (AUC), and Matthews correlation coefficient (MCC), incorporating gene-specific pathogenicity thresholds to enhance predictive precision. Evolutionary conservation was assessed using ConSurf, while structural consequences were examined using UniProt, HOPE, DUET, PyMOL, and RING. Nine top-performing tools—MutPred, MetaRNN, REVEL, MutScore, SNPred, BayesDel, ClinPred, AlphaMissense, and DeepSAV—achieved accuracies exceeding 91% and correctly classified all 19 functionally validated pathogenic variants. These tools consistently predicted 15 VUS as pathogenic, with 14 located within the methyl-CpG-binding domain (MBD) and one within the NCOR2/SMRT interaction region; all occurred at highly conserved residues (ConSurf score: 9). Structural analyses revealed destabilizing effects through altered hydrophobicity, electrostatic charge, and residue interactions, implicating impaired DNA binding or disrupted co-repressor interactions. This integrative framework, combining high-performance computational prediction with structural modeling, offers a robust approach to reclassifying <i>MECP2</i> VUS and supports improved diagnostic accuracy and personalized care in RTT.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181818","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":"miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder","authors":"Sohair M. Salem,&nbsp;Nora N. Ismaiel,&nbsp;Ammal M. Metwally,&nbsp;Engy A. Ashaat,&nbsp;Maha M. Kobesiy","doi":"10.1007/s12031-025-02390-z","DOIUrl":"10.1007/s12031-025-02390-z","url":null,"abstract":"<div><p>One of the well-studied epigenetic regulators is miRNA (miRNA) which plays critical roles in gene regulation and has been implicated in autism spectrum disorder (ASD) pathology, particularly through their involvement in neuroinflammation and neuronal regulation. MiR-146A and miR-146B are of special interest due to their dysregulation in ASD. Epigenetic modifications, such as promoter methylation, and genetic variations in miRNAs can influence their expression and function, yet their roles in ASD remain unclear. This study aimed to investigate promoter methylation patterns and sequence variations in miR-146A and miR-146B to evaluate their potential contributions to ASD. The study included Egyptian patients with ASD (ages 5–16 years) diagnosed using DSM-V criteria and assessed for severity using the Childhood Autism Rating Scale (CARS). DNA was extracted from peripheral blood samples of 93 autistic patients and 44 age-matched controls. Methylation-specific PCR (MSP) was used to analyze promoter methylation of miR-146A and miR-146B, while Sanger sequencing was employed to detect sequence variations in these genes and their flanking regions. Statistical analyses included independent <i>t</i>-tests, ANOVA, ROC curve, and Pearson correlation. No significant differences in promoter methylation levels of miR-146A and miR-146B were observed between ASD cases and controls or among severity subgroups (<i>P</i> &gt; 0.05). Sequence variation analysis identified no significant differences in the distribution of common SNPs (<i>rs2910164</i> and <i>rs2224374</i>). However, a novel miR-146A upstream variant (C/A at 5:160,485,254) was discovered in one case with autism. Methylation and common genetic variations in miR-146A and miR-146B are unlikely to play significant roles in ASD in this population. The discovery of a novel upstream variant highlights the potential importance of regulatory regions in miRNA function. Further studies with larger cohorts and functional validation are recommended.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181803","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":"RGS2-Related Non-coding Interaction Network Modulates the NF-Kappa B Signaling Pathway in MS Patients: A Systems Biology Investigation","authors":"Parisa Forouzanfar,&nbsp;Mohammad Hashemian,&nbsp;Mojdeh Mahmoudian,&nbsp;Melika Khorsandi,&nbsp;Mohammad Rezaei,&nbsp;Mansoureh Azadeh","doi":"10.1007/s12031-025-02413-9","DOIUrl":"10.1007/s12031-025-02413-9","url":null,"abstract":"<div><p>Multiple sclerosis (MS) is the most common chronic inflammatory disease affecting the brain and spinal cord, with approximately 2.8 million cases globally. This study analyzed high-throughput MS datasets to identify dysregulated RNAs and visualized novel RNA regulatory networks to uncover non-coding interactions in MS-related signaling pathways. High-throughput gene expression datasets were analyzed in R Studio to identify dysregulated mRNAs in MS patients. miRNA, lncRNA, and protein interactions were explored using miRWalk and lncRRIsearch. Pathway enrichment analysis was performed via Enrichr and KEGG, and qRT-PCR validated the gene expression results. RGS2 was found to be significantly upregulated in both microarray (logFC: 1.7667, adj.P. Value: 0.0079) and qRT-PCR analyses (logFC: 4.547, <i>p</i>-value &lt; 0.0001). Similarly, the lncRNAs NCK1-DT (logFC: 2.155, <i>p</i>-value: 0.0132) and ASH1L-AS1 (logFC: 3.345, <i>p</i>-value &lt; 0.0001) exhibited elevated expression in MS samples, suggesting a regulatory impact on RGS2 expression levels. The marked changes in the expression of RGS2, NCK1-DT, and ASH1L-AS1 in MS patients compared to normal samples position them as promising diagnostic biomarkers. Additionally, RGS2 and its associated proteins have been implicated in modulating the NF-Kappa B signaling pathway. MiR-4638-3p was identified to directly downregulate RGS2 expression, while miR-4525 influences the expression of RGS2 and ASH1L-AS1 within a competing endogenous RNA (ceRNA) network. NCK1-DT and ASH1L-AS1 are the two novel diagnostic biomarkers of MS. Mentioned lncRNAs might affect the normal regulatory mechanisms of “NF-Kappa B signaling pathway” through direct and indirect interaction with mRNA RGS2.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145223","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":"Salivary Circadian Gene Expression as a Molecular Indicator of Early Cognitive Impairment in Shift Workers: A Cross-Sectional Study of 300 Adults","authors":"Adam Karim,&nbsp;Youssef Rayan,&nbsp;Ziad Amir,&nbsp;Malik Samir,&nbsp;Tariq Jamal,&nbsp;Karim Adnan,&nbsp;Omar Fares,&nbsp;Kareem Zane,&nbsp;Samir Tarek,&nbsp;Amir Nasir,&nbsp;Rami Khalid,&nbsp;Zeyad Khalil,&nbsp;Yasin Rafiq,&nbsp;Idris Nader","doi":"10.1007/s12031-025-02417-5","DOIUrl":"10.1007/s12031-025-02417-5","url":null,"abstract":"<div><p>This cross-sectional study explored the potential utility of salivary circadian gene expression as a non-invasive biomarker for early cognitive impairment in shift workers. Three hundred participants aged 25 to 55 were categorized into cognitively impaired shift workers (MoCA &lt; 26, <i>n</i> = 100), cognitively intact shift workers (<i>n</i> = 100), and non-shift working controls (<i>n</i> = 100). Saliva samples collected at 07:00 and 19:00 were analyzed for mRNA expression of <i>PER1</i>, <i>BMAL1</i>, and <i>CLOCK</i> using qRT-PCR. Shift workers with cognitive impairment showed significantly attenuated diurnal variation in gene expression, with reduced evening levels of <i>BMAL1</i> and <i>PER1</i> compared to both control groups (<i>p</i> &lt; 0.001). Evening <i>BMAL1</i> expression was independently associated with cognitive status (OR 2.14, 95% CI 1.62–2.85), achieving an AUC of 0.876 (81.3% sensitivity, 78.0% specificity). A combined three-gene panel modestly improved diagnostic accuracy (AUC 0.913). These preliminary findings suggest that alterations in salivary circadian gene expression, particularly in <i>BMAL1</i>, may hold promise as a molecular indicator of early neurocognitive changes in shift-working populations.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110532","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":"Therapeutic Potential of products derived from Pluchea lanceolata for Alzheimer’s Disease Treatment","authors":"Asad Syed,&nbsp;Abdallah M. Elgorban,&nbsp;Ali H. Bahkali,&nbsp;Shifa Wang,&nbsp;Ling Shing Wong,&nbsp;Bikram Dhara,&nbsp;Daniel Ejim Uti,&nbsp;Esther Ugo Alum,&nbsp;Item Justin Atangwho","doi":"10.1007/s12031-025-02409-5","DOIUrl":"10.1007/s12031-025-02409-5","url":null,"abstract":"<div><p>AD is a neurodegenerative disorder and is associated with the presence of amyloid-β plaques and neurofibrillary tangles leading to net loss of neurons, which demonstrates an urgent unmet need to develop new human health therapies based on the fundamental mechanisms of oxidative stress and neuroinflammation. This work is a computational assessment of the potential use of neolupenol, a triterpenoid produced in <i>Pluchea lanceolata</i>, as a pharmacologically active compound that exerted its beneficial effect through the modulation of the Keap1-Nrf2 axis, one of the central regulators of the antioxidant response. Using an integrated approach that combined network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we identified neolupenol as a high-affinity Keap1-binding molecule capable of activating the Nrf2-mediated neuroprotective pathway. Virtual screening of 25 phytochemicals from <i>Pluchea lanceolata</i> (retrieved from the PubChem database) with customized filters revealed neolupenol as the top candidate, showing strong binding affinity (− 8.22 kcal/mol; Ki = 1.45 µM) toward the Keap1 Kelch domain (PDB ID: 2FLU). The docked complex demonstrated hydrogen bonds with VAL463 (2.17 Å), THR560, and ILE559, along with hydrophobic interactions involving CYS513, ALA366, and VAL514, which collectively stabilized the ligand at the Neh2-binding interface. Network pharmacology yielded 30 of such common targets of AD-neolupenol (e.g., GSK3B, CASP3, TNF, and BACE1), enriched in pathways such as amyloid processing, tau phosphorylation, oxidative stress response, and lipid metabolism (FDR-adjusted <i>p</i> &lt; 0.0001). Complex stability was verified by MD simulations (100 ns): RMSD of the backbone 2.34–3.84 = 2.34 Å, unchanged radius of gyration (17.8–18.0 Å), and stable inter-hydrogen bonding. Residues VAL561, PHE577, and SER602 were found to have an interaction occupancy of &gt; 70%, providing a basis of dynamic stability. The triterpenoid cavity appeared in neolupenol contributing to pleasant PK, the ability to herald the blood–brain barrier, and suboptimal toxicity. These results position neolupenol as a potent, multi-target neuroprotective agent that disrupts Keap1–Nrf2 interaction, promoting Nrf2 nuclear translocation and antioxidant gene activation. Future work warrants in vivo validation of its efficacy in mitigating AD pathology and clinical translation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110533","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":"Integrin CD11b Alleviates Cerebral Ischemia/Reperfusion Injury via a Mechanism Involving Microglia/Macrophage Polarization","authors":"Gui-Nan Jiang,&nbsp;Qiu-Yue Lin,&nbsp;Xiang-Bo An,&nbsp;Wei-Jia Yu,&nbsp;Jie Bai,&nbsp;Xin Yu,&nbsp;Feng Wang,&nbsp;Hui-Hua Li","doi":"10.1007/s12031-025-02414-8","DOIUrl":"10.1007/s12031-025-02414-8","url":null,"abstract":"<div><p>The polarization of microglia/macrophages is crucial for maintaining the neuroinflammatory response during cerebral ischemia/reperfusion (I/R) injury. Integrin CD11b is implicated in the processes of neuroinflammation, immune regulation, and nerve injury repair. However, its role in microglia- and macrophage-mediated neuroinflammation during cerebral I/R injury remains poorly understood. Wild-type (WT), CD11b knockout (KO), or neutralizing antibody-treated mice were subjected to a transient cerebral artery I/R injury (tMCAO) model. CD11b expression was detected by qPCR, immunofluorescence, and western blotting. Histopathological features were evaluated by H&amp;E and Nissl staining, ROS production was detected by DHE staining, neuronal apoptosis was detected by TUNEL assays, and microglia polarization was evaluated by immunofluorescence staining. We discovered that CD11b was significantly increased in the ischemic penumbra following tMCAO. CD11b KO significantly alleviated tMCAO-induced infarct, neurological deficits, oxidative stress, and neuronal apoptosis in the ischemic penumbra. Moreover, CD11b KO significantly enhanced the anti-inflammatory phenotype transition of microglia/macrophages, leading to accelerated inflammation resolution. Furthermore, pharmacological blockade of CD11b demonstrated a protective effect similar to that of CD11b KO. Meanwhile, CD11b deficiency significantly inhibited the activation of p-p65/p-STAT1 signaling pathway and upregulated p-STAT6 expression. In conclusion, CD11b protects against cerebral I/R injury by modulating microglial and macrophage polarization, thereby reducing subsequent neuroinflammation and neuronal death. Our findings suggest that CD11b intervention could be a potential therapeutic strategy for acute cerebral ischemic stroke.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090328","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":"Cognitive and Behavioral Effects of Chronic Tartrazine Use in vivo: An Assessment Within and Above the Acceptable Daily Intake","authors":"André Fellipe Freitas Rodrigues,&nbsp;Maisa Vitória Santos Sales,&nbsp;Gabriela Haro de Melo,&nbsp;Vinicio Berti da Silva,&nbsp;Graziela Garrido Mori","doi":"10.1007/s12031-025-02410-y","DOIUrl":"10.1007/s12031-025-02410-y","url":null,"abstract":"<p>The use of dyes is a common practice in several industrial sectors to increase the attractiveness of the merchandise. Tartrazine is a synthetic yellow dye used in various food products; it contains an azo bond in its composition. The present study aimed to analyze whether the chronic consumption of Tartrazine promotes changes in cognitive and behavioral parameters in vivo. A total of 40 Wistar rats (50% male and 50% female) were divided into three experimental groups: control group (CG) (<i>n</i> = 16), group treated with a dose within the acceptable daily intake (ADI), corresponding to 7.5 mg/kg/day (NEG) (<i>n</i> = 16), and group treated above the recommended value at a dose of 15 mg/kg/day (AEG) (<i>n</i> = 8). Tartrazine was administered via gavage daily for 10 months. Finally, the rats were subjected to the open field test (OFT), elevated plus maze (EPM), and object recognition test (OR) to evaluate their motor activity, anxiety, and long-term memory, respectively. All data were subjected to statistical analysis using ANOVA or Kruskal-Wallis tests, with a significance level of 5% (<i>p</i> &lt; 0.05). There were no statistically significant changes in locomotor behavior (<i>p</i> = 0.351) and anxiety levels (<i>p</i> = 0.305) of the animals in either group. However, the group treated within the ADI demonstrated impairment in long-term memory (<i>p</i> &lt; 0.001). Given this, it can be considered that prolonged use of Tartrazine, even within the ADI value limits, can cause mild impairment of certain cognitive functions.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079022","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":"Correction: Urolithin A Enhances Tight Junction Protein Expression in Endothelial Cells Cultured In Vitro via Pink1-Parkin-Mediated Mitophagy in Irradiated Astrocytes","authors":"Gengxin Lu,&nbsp;Junyu Wu,&nbsp;Zhihui Zheng,&nbsp;Zhezhi Deng,&nbsp;Xue Xu,&nbsp;Xintian Li,&nbsp;Xiaoqiu Liang,&nbsp;Weiwei Qi,&nbsp;Shifeng Zhang,&nbsp;Yuemin Qiu,&nbsp;Minping Li,&nbsp;Junjie Guo,&nbsp;Haiwei Huang","doi":"10.1007/s12031-025-02346-3","DOIUrl":"10.1007/s12031-025-02346-3","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073736","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":"Antiepileptic and Neuroprotective Biochemical Actions of Sabinene Prevent the Development of Pentylenetetrazol-Induced Seizures and Neuropsychiatric Comorbidities in Mice","authors":"Grant Alumona,&nbsp;Benneth Ben-Azu,&nbsp;Daniel T. Esuku,&nbsp;Bienose S. Chijioke,&nbsp;Akhator J. Amenotie,&nbsp;Ayereoghene S. Moses,&nbsp;Faith B. Friday,&nbsp;Emuesiri G. Moke,&nbsp;Obukohwo M. Oyovwi,&nbsp;Ekpekuro Abo,&nbsp;Abayomi M. Ajayi","doi":"10.1007/s12031-025-02404-w","DOIUrl":"10.1007/s12031-025-02404-w","url":null,"abstract":"<div><p>Epilepsy is a long-term neurological disorder that leads to disability with neuropsychiatric comorbidities. Studies have shown that neurochemical imbalances involved in the disease are linked to heightened oxidative and inflammatory pathways, which significantly affect the severity of the disease. As a result, substances that have antioxidant and anti-inflammatory effects might help in managing the condition. Hence, this study investigated the effects of sabinene, a natural monoterpene in essential oils, against pentylenetetrazol-induced seizure kindling and neuropsychiatric comorbidities in mice, revealing insights into the neurochemical, antioxidant, and anti-inflammatory biochemical mechanisms involved. Male Swiss mice in adulthood were pretreated with sabinene (5 and 10 mg/kg) or diazepam (3 mg/kg) 30 min prior to pentylenetetrazol-induced seizures, with injections administered every other day for 28 days. We conducted behavioral assessments using a Racine scale (0–6) and evaluated comorbidities such as cognitive impairments and depression. Neurochemical, antioxidant and anti-inflammatory biochemical mechanisms of the antiepileptic effect of sabinene against pentylenetetrazol-induced kindling were analyzed in the prefrontal cortex and hippocampus, two brain regions largely involved in the disease’s onset and development. Sabinene inhibits pentylenetetrazol-induced seizures evidenced by the reduced frequency and severity of seizure episodes. Sabinene decreases motor activity, reverses pentylenetetrazol-associated spatial/non-spatial memory deficits, increases sociability, and lowers the depressive symptoms. These behavioral changes reversed by sabinene were accompanied by reduced prefrontal-hippocampal glutamate release and increase GAD enzyme. Consistent with this, sabinene elevated IL-10 in both brain areas while also increasing the levels of prefrontal pro-inflammatory cytokines, such as TNF-α and IL-1β. However, sabinene reduced TNF-α and IL-1β in the hippocampus, as well as oxidant markers (malondialdehyde, nitrite), and increased antioxidant systems in both brain regions compared to the pentylenetetrazol cohorts. Overall, sabinene’s antiepileptic and neuroprotective effects include modulating neurotransmitter imbalances, inhibiting oxidative stress, and modulating cortical neuroimmune dysfunction.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062300","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":"Serum Metabolomic Profiling in Possible Early-Stage Multiple Sclerosis: A Targeted 1H-NMR Comparison of OCB Type 1 and Type 2 Patterns","authors":"Pınar Şengül,&nbsp;Ahmet Tarık Baykal,&nbsp;Mustafa Serteser","doi":"10.1007/s12031-025-02407-7","DOIUrl":"10.1007/s12031-025-02407-7","url":null,"abstract":"<div><p>Oligoclonal band (OCB) analysis in cerebrospinal fluid (CSF) remains a cornerstone for the early diagnosis of multiple sclerosis (MS), with recent criteria highlighting the κ-free light chain (κ-FLC) index as a sensitive marker of intrathecal immunoglobulin synthesis. However, both approaches rely on lumbar puncture. To address the need for less invasive tools, this study employed proton nuclear magnetic resonance (¹H-NMR)-based serum metabolomics to explore whether peripheral metabolic signatures can distinguish immunophenotypic subgroups, namely OCB Type 1 and Type 2, in patients with suspected early-stage MS. To investigate whether targeted proton nuclear magnetic resonance (¹H-NMR) serum metabolomics can differentiate between individuals with OCB Type 1 (no intrathecal synthesis) and OCB Type 2 (definite intrathecal synthesis), as a step toward non-invasive metabolic stratification in possible early-stage MS. Serum samples (n = 49) were classified by OCB profile and analysed using targeted ¹H-NMR spectroscopy. All spectra were acquired at 298 K on a Bruker Avance Neo 600 MHz spectrometer. Metabolites were identified using Bruker BioRefCode libraries, and absolute quantification was performed using the ERETIC (Electronic Reference To access In vivo Concentrations) signal. Statistical analysis included age-adjusted univariate tests (t-test or Wilcoxon rank-sum, depending on normality) with false discovery rate (FDR) correction, followed by multivariate analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), variable importance in projection (VIP) scores, and ROC-AUC permutations using the pROC package in R. Of the quantified metabolites, Leucine emerged as a robust differentiator, showing significant elevation in OCB Type 2 after both age adjustment and multiple testing correction (p = 0.025, FDR-adjusted; VIP = 2.38; AUC = 0.74), and correlating moderately with the IgG index (r = 0.32, p = 0.026). Histidine, Glycine, Sarcosine, and Succinic acid met VIP &gt; 1.5 thresholds but did not survive FDR correction and are therefore reported as exploratory candidates. This pilot study identifies Leucine as a promising serum biomarker candidate for early intrathecal immune activity. Although additional metabolites showed potential, their findings remain exploratory due to statistical limitations. These results highlight the potential of targeted serum metabolomics as a non-invasive adjunct in early MS risk stratification and support further validation studies incorporating κ-FLC data and longitudinal follow-up.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062299","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}