Journal of Molecular Neuroscience最新文献

{"title":"Clinical Study on the Combined Use of Tadalafil and Epalrestat in the Treatment of Diabetic Neurovascular Erectile Dysfunction","authors":"Peng Sun,&nbsp;Miao Yu","doi":"10.1007/s12031-026-02504-1","DOIUrl":"10.1007/s12031-026-02504-1","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to evaluate the clinical efficacy of tadalafil combined with epalrestat in the treatment of diabetic neurovascular erectile dysfunction (ED). Eighty patients diagnosed with diabetic neurovascular ED admitted to between January 2022 and October 2024 were randomly allocated into two groups (<i>n</i> = 40 each). The control group received tadalafil monotherapy, while the observation group was additionally treated with epalrestat. Both regimens lasted 12 weeks. Outcomes assessed pre- and post-treatment included International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), modified Sexual Life Quality Questionnaire (mSLQQ-QoL), penile hemodynamic parameters [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and serum markers of endothelial function [endothelin-1 (ET-1), von Willebrand factor (vWF), and asymmetric dimethylarginine (ADMA)]. Treatment safety was also evaluated. Post-treatment, both groups showed significant improvements in IIEF-5 scores, proportion of EHS grade III-IV, and mSLQQ-QoL scores, with greater changes observed in the combination group (<i>P</i> &lt; 0.05). The combination group also demonstrated higher PSV and RI, and lower EDV, ET-1, vWF, and ADMA levels than the control group (<i>P</i> &lt; 0.05). No drug-related adverse events occurred in either group (<i>P</i> &gt; 0.05). Tadalafil combined with epalrestat therapy for diabetic neurovascular ED can synergistically improve erectile function, erection hardness, sexual life quality, penile hemodynamics, and vascular endothelial function, with good safety and no increased risk of drug-related adverse events.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147642584","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":"Akira Arimura Foundation Akira Arimura Foundation 2027–2028 Young Investigator Grant Application Procedures","authors":"","doi":"10.1007/s12031-026-02517-w","DOIUrl":"10.1007/s12031-026-02517-w","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621427","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":"Striatal Dysregulation of Angpt2 and Circadian Gene Expression in a Rotenone Rat Model of Parkinson’s Disease","authors":"Dalia Y Al Saeedy,&nbsp;Elisa Hawkins,&nbsp;Mikhail G Dozmorov,&nbsp;Ohm Tripathi,&nbsp;Sina Mahdiani,&nbsp;Fay M Jahr,&nbsp;Ola AlAzzeh,&nbsp;Laxmikant S. Deshpande,&nbsp;Joseph L. McClay","doi":"10.1007/s12031-026-02506-z","DOIUrl":"10.1007/s12031-026-02506-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Rotenone is a naturally-occurring isoflavone that is used as a pesticide. Rotenone is also administered to rats to induce nigrostriatal dopaminergic neuron loss in an established model of Parkinson’s Disease (PD). However, the molecular mechanisms linking rotenone action to the emergence of PD-like phenotypes are poorly understood. Here, we characterize rotenone-induced gene dysregulation in the striatum. Male Lewis rats at 12–14 months received rotenone injected at 3 mg/kg, i.p. once daily for nine days. Behavioral effects of rotenone were verified using the bar test for catalepsy. RNA sequencing was carried out on RNA extracted from the striatum of rats receiving the full course of Rotenone treatment and vehicle-treated controls. Illumina PE150 sequencing to 30 M clusters per sample revealed several hundred differentially expressed genes (DEGs) at FDR &lt; 5%. These included Dopa decarboxylase (<i>Ddc</i>), which encodes an important enzyme in dopamine production, and Angiopoietin 2 (<i>Angpt2</i>), a gene previously implicated in analysis of post-mortem PD brain. Pathway analysis of top findings identified the Circadian Clock System as enriched with rotenone DEGs. Circadian and sleep dysfunction is a known feature of PD. We validated the differential expression of two circadian genes via quantitative PCR: downregulation of Period 3 (<i>Per3</i>) and upregulation of the aryl hydrocarbon receptor nuclear translocator-like (<i>Arntl</i>). Overall this study represents a first look at striatal dysregulation of gene expression in the established rotenone PD model and indicates that further study of circadian gene dysregulation in this model may be fruitful.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-026-02506-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589317","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 Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer’s and Parkinson’s Disease","authors":"Sudarshan Ramanan,&nbsp;Gail V. W. Johnson","doi":"10.1007/s12031-026-02514-z","DOIUrl":"10.1007/s12031-026-02514-z","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders. Within the scope of neurodegenerative disorders, the Bcl-2 associated athanogene (BAG) family proteins and associated interactors have been a key area of focus. The BAG family is a group of proteins that contain at least one evolutionarily conserved BAG domain. Despite this similarity, their interactions and functions can vary widely. So far, research has predominantly scrutinized individual BAG proteins, rather than explore potential cooperative actions among family members. Some BAG family members may function together thereby indicating potential interactions within this family. Although connections among BAG members have been observed, their role in neurodegenerative disorders, such as AD and PD, remains largely uncharacterized. This mini review explores the common pathways, intersections, and differences within these interactions as well as their link to AD and PD. Using computational techniques to mine transcriptomic data, several groupings of pathways that these BAG family members are involved in were identified in the context of AD and PD. Understanding these pathways and their relationships may uncover potential gaps in current research and help identify novel therapeutic targets for the treatment of these neurodegenerative diseases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589310","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":"Circ-find-0001774 Modulates Parkinson’s Disease via miR-153-3p: Mechanistic Insights and Therapeutic Implications","authors":"Ronglan Zhu,&nbsp;Jie Chen,&nbsp;Tao Song,&nbsp;Yun Yang,&nbsp;Chaoyang Zhou,&nbsp;Zhiping Xie,&nbsp;Min Yuan,&nbsp;Jianzhong Zhang","doi":"10.1007/s12031-026-02509-w","DOIUrl":"10.1007/s12031-026-02509-w","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to investigate how circ-find-0001774 regulates miR-153-3p in Parkinson’s disease (PD).</p><h3>Methods</h3><p>We first validated the targeting relationship between circ-find-0001774 and miR-153-3p using dual-luciferase reporter assays, excluding any association with let-7a-5p. Next, we constructed a circ-find-0001774 overexpression vector and transfected it into MN9D dopaminergic neurons, confirming transfection efficiency by qPCR. In vitro, we induced a PD cell model with 100 µmol/L MPP+ iodide for 24 h and assessed cell proliferation using CCK-8, apoptosis via flow cytometry, and miR-153-3p and LC3Ⅱ/Ⅰ protein levels by qPCR and Western blotting. In vivo, we established a mouse PD model by daily intraperitoneal injection of 18 mg/kg MPTP for seven days, evaluating motor function through behavioral tests, observing brain pathology via HE staining, and analyzing miR-153-3p and β-catenin protein levels by qPCR and Western blotting.</p><h3>Results</h3><p>Dual-luciferase assays confirmed a specific targeting interaction between miR-153-3p and circ-find-0001774. In vitro, circ-find-0001774 overexpression significantly enhanced cell proliferation, reduced apoptosis and decreased miR-153-3p and LC3Ⅱ/Ⅰ protein expression levels. In vivo, circ-find-0001774 overexpression notably ameliorated motor deficits in the mouse PD model mitigated neurodegeneration, decreased miR-153-3p level and increased β-catenin protein expression levels.</p><h3>Conclusion</h3><p>Our study reveals that circ-find-0001774 modulates miR-153-3p, mainly through the Wnt/β-Catenin signaling pathway, suggesting its therapeutic potential for PD. These findings provide novel insights and experimental foundations for further developing PD treatment strategies.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571573","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":"Docosahexaenoic Acid Modulates Autophagy and Confers Neuronal Resilience under Hypoxia–Reoxygenation Stress","authors":"Francis Zamora,&nbsp;Manuel L. Montero,&nbsp;Jo-Wen Liu,&nbsp;Viet Hoang Dinh,&nbsp;Johnny D. Figueroa,&nbsp;Marino A. De León","doi":"10.1007/s12031-026-02512-1","DOIUrl":"10.1007/s12031-026-02512-1","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia dramatically worsens neuronal death after injuries and strokes, as neurons rely heavily on oxidative phosphorylation for energy. This study investigated the effects of docosahexaenoic acid (DHA) in reducing cell death in nerve cells. Neuron-like cells, nerve growth factor-differentiated PC12 (NGFDPC12) cell cultures, with or without DHA pretreatment, were exposed to hypoxic conditions (0.5% O₂) for 12 to 48 h, followed by reoxygenation. Results showed that hypoxia caused a significant increase in the stress-response gene HIF-1α, with mRNA levels rising 5.47- and 6-fold at 24 and 48 h, respectively, compared to normoxic controls. Similarly, the pro-apoptotic gene BNIP3 was elevated 3.37- and 2.9-fold at the same time points. After 24 h of hypoxia, cells showed significant reactive oxygen species (ROS) buildup and displayed apoptotic features. The expression of fatty acid-binding protein 5 (FABP5), which is involved in responding to oxidative stress, also increased under hypoxic conditions. Treatment with DHA or rapamycin significantly improved cell viability after hypoxic exposure. To determine whether DHA protects by activating autophagy, we measured the expression of critical autophagy-related genes Atg5, Atg7, and Atg12. Hypoxia suppressed Atg5 and Atg7 expression; however, DHA restored and markedly increased the levels of Atg5, Atg7, and Atg12 beyond those in normoxic conditions. Immunoblot analysis supported these findings, showing higher levels of phosphorylated Beclin-1 and conjugated LC3, two key autophagy markers. These findings support our prior research, suggesting that DHA’s neuroprotective effects during hypoxia may involve the activation of autophagy pathways, highlighting its potential as a therapeutic strategy.</p>\u0000 <p><b>Impact Statement</b></p>\u0000 <p>This study reveals that docosahexaenoic acid (DHA), an omega-3 fatty acid abundant in the brain, enhances neuronal resilience to hypoxia–reoxygenation injury by restoring autophagy function and limiting oxidative stress. These findings uncover a previously underappreciated role for DHA as a modulator of redox-sensitive autophagy pathways and suggest potential therapeutic strategies for ischemic and metabolic neurodegenerative disorders.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571614","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":"Enhancing Parkinson’s Disease Staging: An Integrative Deep Learning Framework for Multimodal Feature Selection","authors":"Sk. Wasim Akram,&nbsp;Chidananda K","doi":"10.1007/s12031-026-02492-2","DOIUrl":"10.1007/s12031-026-02492-2","url":null,"abstract":"<div><p>Parkinson’s disease (PD) affects 10 million globally, with accurate staging essential for personalized treatment planning. Current UPDRS assessments achieve &lt; 93% accuracy due to subjective clinical judgment and unimodal data limitations, failing to capture complex genetic-neuroimaging-clinical interactions driving disease heterogeneity. This study introduces MAFNet, a novel deep learning framework pioneering Iterative Adaptive Vold-Kalman Filter (IAVKF) temporal denoising, Accelerated Binary Particle Swarm Optimization (ABPSO) swarm feature selection, Multilayer Perceptron-Lagrangian Support Vector Machine (MLP-LSVM) classification, and Graph-Attention Based Multimodal Fusion Network (GAMF). Applied to PPMI cohort (200 patients) with genetic SNPs (50), neuroimaging voxels (1,024), and UPDRS-III scores, the end-to-end pipeline delivers 97.6% accuracy, 98.2% precision, 96.8% recall, and 97.3% F1-score—outperforming CNN (92.4%), Autoencoder (90.8%), InceptoFormer (96.6%), and HCT (97.0%). IAVKF boosts SNR + 15.2dB (+ 2.9% accuracy vs. PCA/t-SNE); ABPSO reduces 1,276→340 features (73% reduction); regularization cuts overfitting gap to 0.9% (vs. 4.2% baseline). SHAP interpretability validates clinical plausibility (top predictors: LRRK2 SNPs, UPDRS-III tremor, hippocampal volume). Five-fold CV confirms stability with the Indian cohort external validation. Real-time inference (0.2s/patient, RTX 3090) enables clinical deployment. Future scope includes longitudinal temporal modelling, modality-agnostic fusion, edge deployment, federated learning, and extension to Alzheimer’s/ALS. MAFNet transforms PD staging from subjective assessments to objective precision medicine, enabling biomarker discovery, progression forecasting, and personalized therapies across diverse global populations.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571627","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":"The Impact of Early-Life Seizures on the Maturation of Corticohippocampal Frequency Coordination","authors":"Caleb R. Weinstein,&nbsp;Connor R. Dickson,&nbsp;Natalie Cashen,&nbsp;Gregory L. Holmes,&nbsp;Jeremy M. Barry","doi":"10.1007/s12031-026-02488-y","DOIUrl":"10.1007/s12031-026-02488-y","url":null,"abstract":"<div>\u0000 \u0000 <p>Children who develop epilepsy early in life are at high risk for hippocampal-dependent learning and memory impairments. Evidence suggests that seizures in early life impact learning and memory by interfering with neural oscillations in the entorhinal cortex–hippocampal circuit, thereby altering coordination within and between these regions at specific frequencies. However, several questions remain about the initiation and duration of this circuit discoordination as a result of early-life seizures (ELS). It remains unknown whether circuit discoordination is ELS model specific, if these effects are detectable immediately after seizure and are permanent, or if they are altered over the course of development. We hypothesize that ELS impairs corticohippocampal synaptic signaling at specific CA1 and dentate gyrus (DG) dendritic compartments, that these impairments arise directly after seizure induction and endure into adulthood. We used high-density laminar silicon probes spanning the CA1 and DG somatodendritic axes to assess theta and gamma spectral properties, current source density (CSD), and phase–amplitude coupling (PAC) at multiple phase bandwidths in Control (CTL) rats or ELS rats that experienced recurrent flurothyl-induced seizures as pups. Rats were evaluated at two ages: juvenile (P23) and adult (&gt;P90). ELS adults exhibited oscillation properties similar to juveniles, suggesting a process of post-ELS dysmaturation with age. PAC results revealed that across the DG somatodendritic axis, ELS adults and ELS juveniles both exhibited an absence of slow gamma coupling. In contrast, ELS juvenile CA1 slow gamma coupling was intact, but was abolished in ELS adults. These results suggest that while ELS effects in the DG were immediate and permanent, CA1 effects occurred over a longer timescale during development. Lastly, our data shows a timecourse for normal CA1 and DG synaptic input frequency coordination that is already in place in CTL juveniles at P23, correlating with the fraction of mature dendrites. The results demonstrate that PAC between theta and gamma oscillations can serve as a proxy for the efficacy of synaptic-dendritic processes underlying the coordination of local and distributed networks. We highlight a process of post-seizure dysmaturation, distinguishing between early ELS effects and their long-term developmental consequences within subfields of the corticohippocampal circuit.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147562009","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":"A Causal Association Study Between Brain Imaging Features and the Risk of Large Artery Atherosclerosis: A Two-sample Mendelian Randomization Study","authors":"Weiran Li,&nbsp;Jinjian Li,&nbsp;Wei He,&nbsp;Xu Wang,&nbsp;Dexi Zhao","doi":"10.1007/s12031-026-02516-x","DOIUrl":"10.1007/s12031-026-02516-x","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke (IS) is a complex disease influenced by genetic and environmental factors, large artery atherosclerosis (LAS) has the highest proportion among the three subtypes of IS. Neuroimaging is an important examination for ischemic stroke. This study aims to systematically evaluate the causal relationships between various neuroimaging features and LAS risk using Mendelian randomization (MR). We performed a two-sample MR analysis using genetic data from large-scale genome-wide association studies. Exposure data included structural MRI, diffusion tensor imaging, and resting-state fMRI features. Outcome data were from GWAS on LAS. Inverse variance weighting was the primary analytical method, supplemented by sensitivity analyses. A total of 186 imaging features showed causal associations with LAS risk in genetic prediction. Increased volume in specific brain regions (left middle temporal gyrus, right cerebellum) was associated with higher risk in genetic prediction. Altered white matter microstructure in tracts like the pontine crossing tract and functional connectivity strength within the default mode and salience networks were also causally linked to LAS in genetic prediction. This MR study provides robust genetic evidence that the structural integrity of specific brain regions, white matter pathway efficiency, and functional network connectivity play potential causal roles in LAS pathogenesis. These neuroimaging features hold promise as novel biomarkers for predicting stroke risk and offer new insights into the neural circuit mechanisms of LAS.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147561797","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":"Targeting Maladaptive Memory Circuits in Heroin Addiction: a Review of Non-Pharmacological Interventions for Cognitive Recovery","authors":"Guihua Chen,&nbsp;Yajuan Yao,&nbsp;Fei Li,&nbsp;Zaiman Zhu,&nbsp;Min Li","doi":"10.1007/s12031-026-02493-1","DOIUrl":"10.1007/s12031-026-02493-1","url":null,"abstract":"<div>\u0000 \u0000 <p>Opioid use disorder, notably heroin addiction, is characterized by severe deficits in learning and memory, which contribute critically to high relapse rates. This review synthesizes recent preclinical and clinical evidence positing that addiction pathologically co-opts the brain’s natural memory systems. We focus on dysregulated plasticity within a core network comprising the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), hippocampus (HPC), and basolateral amygdala (BLA). A key advancement is the identification of sparse, stable neuronal ensembles—‘addiction engrams’—within these circuits that physically encode drug-associated memories. We critically evaluate non-pharmacological interventions, including exercise, neuromodulation, and environmental enrichment, for their potential to normalize circuit dynamics and disrupt these maladaptive ensembles. Furthermore, we highlight emerging evidence indicating that the neuroadaptations underlying addiction and treatment response are significantly influenced by sex-specific mechanisms. We conclude that elucidating these sex differences and developing personalized intervention protocols based on individual neural circuitry and temporal dynamics are crucial steps toward effective cognitive rehabilitation in opioid addiction.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147561798","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}