Brain Research Bulletin最新文献

{"title":"Network Toxicology, Molecular Docking, and Molecular Dynamics to Explore the Epilepsy Mechanism Induced by Tetramine Poisoning.","authors":"Ming-Wei Liu, Hui-de Peng, Yu-Fang Cun, Shu-Ji Gao, Yan-Lin Zhu, Xuan Li, Cai-Rui Li","doi":"10.1016/j.brainresbull.2026.111915","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111915","url":null,"abstract":"<p><p>Tetramine poisoning commonly leads to epilepsy, with complex underlying mechanisms and poor treatment outcomes. This study aimed to explore the mechanisms of epilepsy induced by tetramine poisoning via network toxicology and molecular docking approaches. Tetramine poisoning targets were obtained from the SuperPred database, whereas epilepsy-related gene targets were identified through the GeneCards and OMIM databases. The intersection of tetramine targets and epilepsy-related genes revealed candidate targets. A proteinprotein interaction (PPI) network for these candidate targets was constructed via the String platform, after which the core functional modules were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted via the Metascape platform. Additionally, a targetpathway network involving Tetramine and brain injury was constructed via Cytoscape 3.8.2 software, enabling network topology analysis and screening of key components and targets. The results found that a total of 118 candidate targets for tetramine-induced epilepsy were identified. Pathway enrichment analysis indicated that tetramine-induced epilepsy is likely associated with the HIF-1, PI3K-Akt, Ras, Toll-like receptor, chemokine, and neurotrophin signaling pathways. The core targets include SRC, STAT3, HSP90AB1, MMP9, and HIF1A. To verify the above findings experimentally, this study established an epilepsy rat model by intragastric administration of different doses (0.1, 0.25, 0.5mg/kg) of tetramine. The seizure behavior was evaluated using the Racine scoring system, and hippocampal tissues were collected for subsequent tests. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of five core targets, as well as the phosphorylation levels of STAT3, SRC, Akt, and ERK. Immunofluorescence staining was used to observe the expression and distribution of p-STAT3 and HIF1A in brain tissues, and HE staining was used to assess the histopathological changes. The results showed that tetramine induced severe epileptic seizures in a dose-dependent manner. At the same time, the mRNA and protein expression levels of core targets HIF1A, MMP9, HSP90AB1, SRC, and STAT were all upregulated, and the phosphorylation levels of STAT3, SRC, Akt, and ERK were increased. Immunofluorescence and HE staining further confirmed the protein activation and pathological changes induced by tetramine.Network toxicology methods suggest that tetramine may induce epilepsy through multiple targets and signaling pathways. The above experimental results have preliminarily verified the key targets for network toxicology identification. However, the specific mechanism still needs to be further studied and confirmed.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111915"},"PeriodicalIF":3.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856080","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":"Astrocyte-mediated angiogenesis in CNS diseases: mechanisms and therapeutic implications.","authors":"Zhidong He, Ying Mao, Lumei Chi, Jing Sun","doi":"10.1016/j.brainresbull.2026.111914","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111914","url":null,"abstract":"<p><p>Astrocytes are central, yet often underappreciated, regulators of angiogenesis in the central nervous system (CNS), exhibiting a profound context-dependent duality. They can foster restorative vascular repair after ischemic injury while simultaneously driving pathological vessel formation in tumors and other neurological disorders. This review synthesizes current knowledge on astrocyte-mediated angiogenesis across major CNS diseases, critically examining how disease-specific cues-such as hypoxia, tumor-derived factors, or Aβ plaques-are integrated to produce distinct vascular outcomes. We move beyond the binary A1/A2 paradigm to introduce a framework of \"disease-associated astrocyte subsets\" (e.g., ischemia-associated, glioma-associated, and Alzheimer's disease-associated astrocytes), as revealed by emerging single-cell studies. Key mechanisms are dissected, including the tightly regulated VEGF/Ang axis, HMGB1 signaling, the Sonic Hedgehog pathway, and the growing role of exosomal miRNA transfer. A central challenge highlighted is the temporal dichotomy of VEGF action, which transitions from acutely detrimental to beneficial during recovery. We explore therapeutic implications, from promoting reparative angiogenesis in ischemia to inhibiting pathological angiogenesis in glioblastoma. By identifying critical knowledge gaps, we propose future directions-such as astrocyte-specific gene editing and engineered exosomes-that aim to translate these insights into effective, context-specific CNS therapies.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111914"},"PeriodicalIF":3.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856022","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":"Neural Substrates of Apathy in Parkinson's Disease: a systematic review of Structural and Functional Neuroimaging Studies.","authors":"Giulia Marafioti, Laura Culicetto, Carlo Blundo, Carla Susinna, Giovanni Restuccia, Giuseppe Di Lorenzo, Angelo Quartarone, Viviana Lo Buono","doi":"10.1016/j.brainresbull.2026.111922","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111922","url":null,"abstract":"<p><strong>Background: </strong>Apathy is a frequent and disabling non-motor symptom in Parkinson's disease (PD), characterized by diminished motivation, reduced goal-directed behavior, and emotional indifference. Growing evidence suggests that apathy in PD represents a distinct neuropsychiatric syndrome that may coexist with depression and global cognitive impairment, while also showing partially dissociable clinical and neural correlates.</p><p><strong>Objective: </strong>This systematic review aimed to investigate the neural substrates of apathy in PD by synthesizing evidence from structural and functional neuroimaging studies.</p><p><strong>Methods: </strong>Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus for studies assessing apathy in PD through neuroimaging techniques, including structural MRI, resting-state functional MRI, diffusion tensor imaging, PET/SPECT molecular imaging, and connectivity analyses. Apathy severity was evaluated using validated clinical scales, and findings were compared between PD population with and without apathy, as well as healthy controls.</p><p><strong>Results: </strong>Across 16 heterogeneous studies, recurrent findings implicated structural, functional, and molecular alterations within fronto-striatal-limbic networks. However, differences in apathy measures and neuroimaging modalities limit direct comparability across studies and do not support a single unified imaging signature of apathy in PD. Apathetic PD subjects consistently exhibited reduced gray matter volume and altered spontaneous activity in the dorsolateral, inferior frontal gyri, anterior cingulate cortex (ACC), and nucleus accumbens, alongside disrupted functional and structural connectivity in fronto-limbic tracts. These alterations were significantly correlated with apathy severity and, in several studies, remained detectable after accounting for depressive symptoms or global cognitive status. Furthermore, the available findings suggest that apathy in PD may involve heterogeneous neurobiological mechanisms, including variable involvement of frontal, striatal, and limbic circuits; however, current evidence remains insufficient to support firm transmitter-based subtyping or treatment stratification.</p><p><strong>Conclusions: </strong>Current evidence suggests that apathy in PD involves partially dissociable neural correlates across prefrontal, striatal, and limbic systems. However, methodological heterogeneity across studies limits strong generalization, and future harmonized longitudinal studies are needed to clarify which findings are robust and clinically meaningful.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111922"},"PeriodicalIF":3.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856102","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":"Subclinical Gray Matter Damage: Macro- and Microstructural Findings in Stroke-Free Unilateral Middle Cerebral Artery Occlusion Patients.","authors":"Zhenghua Liu, Xinghua Wan, Yu Xiao","doi":"10.1016/j.brainresbull.2026.111919","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111919","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate macrostructural and microstructural damage in the gray matter of stroke-free patients with unilateral middle cerebral artery (MCA) occlusion using three-dimensional T1-weighted imaging (3D T1WI) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequences.</p><p><strong>Method: </strong>A total of 56 patients with unilateral MCA occlusion and 60 age- and sex-matched healthy controls underwent 3.0T MRI with 3D T1WI and NODDI sequences. Voxel-based morphometry was applied to quantify regional brain volumes from 3D T1WI data, while Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were derived from NODDI data. Voxel-wise statistical comparisons assessed differences in regional gray matter volume, cortical thickness, NDI, and ODI between groups.</p><p><strong>Results: </strong>Compared with healthy controls, individuals with unilateral MCA occlusion exhibited significant reductions in global gray matter volume and average cortical thickness. Specifically, unilateral MCA occlusion was linked to more extensive regional gray matter volume decreases. Notably, right MCA occlusion was uniquely associated with volume loss in the hippocampus, parahippocampal gyrus, and limbic system. Microstructural analysis revealed that, relative to controls, patients showed reduced NDI primarily in bilateral white matter tracts and decreased ODI in specific cortical regions of the frontal and occipital lobes.</p><p><strong>Conclusions: </strong>In stroke-free individuals with unilateral MCA occlusion, widespread macrostructural and microstructural damage to the gray matter is observed, affecting bilateral cerebral and cerebellar regions beyond the classic MCA vascular territory. Notably, the limbic system exhibits marked susceptibility, particularly involving the hippocampus, parahippocampal gyrus, and other limbic structures.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111919"},"PeriodicalIF":3.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834122","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":"Rapid sequential activation from A1 to V1 in congenitally blind and sighted subjects.","authors":"Samuel Paré, Sylvain Baillet, Maurice Ptito, Ron Kupers","doi":"10.1016/j.brainresbull.2026.111892","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111892","url":null,"abstract":"<p><p>Tactile information in congenitally blind (CB) individuals is funneled to the visual cortex through both via a fast thalamo-cortical and a strengthened polysynaptic cortico-cortical pathway. Auditory inputs can also activate the visual cortex in CB individuals, but whether these signals rely on the same dual route remains unclear. We used magnetoencephalography (MEG) to map the spatiotemporal dynamics and measure directed functional connectivity between regional brain responses to monaural auditory cues in eight CB and eight sex and age-matched sighted control (SC) participants. In both groups, a distinct sequential activation pattern was observed, initiating in the thalamus 10-20 ms after stimulus onset, followed by auditory cortex (A1) at approximately 35 ms, and visual cortex (V1) at 45-50 ms post-cue. Because monosynaptic cortico-cortical transmission typically occurs within about 10-15 ms, this temporal sequence suggests that auditory inputs reach the visual cortex through a direct, likely monosynaptic pathway between A1 and V1 in both CB and SC participants. Effective connectivity in the alpha band (8-12Hz) was stronger in CB, birectionally between the thalamus and V1 and unidirectionally from A1 to V1, indicating functional strengthening of these pathways in congenital blindness. These findings suggest that, in CB, auditory signals are relayed to the occipital cortex primarily through an enhanced monosynaptic A1-to-V1 pathway that is also present, though weaker, in sighted individuals. This organization contrasts with tactile information processing in CB, which additionally engages a novel thalamo-cortical route to V1. Our results provide MEG-based evidence for a rapid, likely monosynaptic, A1-to-V1 pathway that is strengthened in congenital blindness.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111892"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811318","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":"Targeted inhibition of microglial C5aR1 by PMX205 mitigates post-ischemic stroke neuroinflammation and promotes functional recovery","authors":"Jie Cao ,&nbsp;Saisai Tian ,&nbsp;Zilong Deng ,&nbsp;Jin Xu ,&nbsp;Yangyang Liu ,&nbsp;Xuan Shi ,&nbsp;Lei Bai ,&nbsp;Xiang Li Jr ,&nbsp;Haiying Li","doi":"10.1016/j.brainresbull.2026.111873","DOIUrl":"10.1016/j.brainresbull.2026.111873","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke constitutes the leading cause of death and disability worldwide. Post-stroke neuroinflammation, a major driver of secondary neurodegeneration, has emerged as a priority therapeutic target. Microglia serve as critical initiators of this neuroinflammatory cascade in ischemic stroke. This study employed single-cell RNA sequencing and functional experiments to identify key regulatory factors in microglia following distinct ischemic stroke subtypes, with the goal of translating these findings into therapeutic targets for clinical application.</div></div><div><h3>Methods</h3><div>To identify key regulators in ischemic stroke, we mined and analyzed public single-cell RNA sequencing datasets. Two etiologically distinct stroke models were subsequently established: permanent focal ischemia via distal middle cerebral artery occlusion (dMCAO) and transient ischemia-reperfusion injury using middle cerebral artery occlusion/reperfusion (MCAO/R). <em>C5aR1</em> spatiotemporal expression was quantified through immunofluorescence (cellular localization) and quantitative immunoblotting (temporal dynamics), followed by validation of PMX205-<em>C5aR1</em> binding affinity via rigid-receptor molecular docking. Therapeutic assessment included acute-phase measurements (3d post-stroke): pro-inflammatory cytokines (ELISA), cerebral infarction volume (TTC staining), and co-quantification of neuronal apoptosis/viability (TUNEL/Nissl); alongside chronic functional recovery tracking (14d): motor coordination (rotarod), sensorimotor integration (adhesive removal test), anxiety-like behavior (open field exploration), and spatial working memory (Y-maze spontaneous alternation).</div></div><div><h3>Results</h3><div>Bioinformatics analysis identified significant upregulation of <em>C5aR1</em> in activated microglia following ischemic stroke. This finding was corroborated by spatially resolved immunofluorescence and quantitative immunoblotting; molecular docking confirmed stable PMX205-C5aR1 binding via specific hydrophobic interactions, and subsequent therapeutic intervention with PMX205 profoundly suppressed neuroinflammation (IL-1β/IL-6/TNF-α), reduced cerebral infarction, attenuated neuronal apoptosis, and reversed long-term neurological deficits.</div></div><div><h3>Conclusion</h3><div>Targeted inhibition of C5aR1 by PMX205 represents a therapeutically viable strategy to attenuate neuroinflammatory cascades and improve long-term functional recovery after ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"239 ","pages":"Article 111873"},"PeriodicalIF":3.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637979","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":"The role of indole metabolites derived from gut microbiota in Parkinson's disease: A comprehensive review","authors":"Shuo Meng","doi":"10.1016/j.brainresbull.2026.111775","DOIUrl":"10.1016/j.brainresbull.2026.111775","url":null,"abstract":"<div><div>Emerging evidence suggests that Parkinson’s disease (PD) extends beyond the brain and involves early disturbances along the gut-brain axis. Among the metabolites shaping this communication, bacterial products derived from tryptophan, particularly indole compounds, are gaining attention as key biochemical links between intestinal dysbiosis and neurodegeneration. Multi-omics studies consistently show a reduction in commensal bacteria capable of producing beneficial indoles and an enrichment of <em>Enterobacteriaceae</em> that redirect tryptophan catabolism toward toxic intermediates. This shift disrupts epithelial and blood-brain barrier function and amplifies inflammatory and oxidative stress pathways within the central nervous system. Protective metabolites such as indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-carbinol (I3C) exert antioxidant, barrier-stabilizing, and anti-inflammatory effects through receptors including the aryl hydrocarbon and pregnane X receptors. Conversely, uremic indoles such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS) activate microglia and astrocytes, promote α-synuclein aggregation, and accelerate dopaminergic neuron loss. Together, these findings support a view of PD as a metabolic imbalance between neuroprotective and neurotoxic indoles. Understanding how microbial and host pathways regulate this balance may open opportunities for early diagnosis and targeted interventions that integrate metabolism, immunity, and neuroprotection.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"237 ","pages":"Article 111775"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154363","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":"The salience network, depression, and exercise dependence in middle-aged and older adults: A structural MRI study","authors":"Feifei Zhang ,&nbsp;Yingbo Shao ,&nbsp;Zhiyun Jia ,&nbsp;Xiaochun Wang","doi":"10.1016/j.brainresbull.2026.111770","DOIUrl":"10.1016/j.brainresbull.2026.111770","url":null,"abstract":"<div><h3>Background</h3><div>Exercise guidelines encourage middle-aged and older adults to engage in physical activity for its health benefits. However, continuous excessive exercise can also lead to physiological and psychological symptoms, often called exercise dependence. The precise brain pathways underlying exercise dependence and depression in older individuals remain unclear.</div></div><div><h3>Methods</h3><div>This study included 79 participants exhibiting symptoms of exercise dependence and 54 healthy participants who engaged in regular exercise without symptoms. Initially, paper-based questionnaires were used to evaluate participants' overall health and symptoms of exercise dependence. Subsequently, non-negative matrix factorization and Kullback–Leibler divergence-based similarity analysis were employed to identify structural brain networks. At the same time, a two-sample T-test was conducted to assess group differences. Finally, partial correlation and mediation analyses were performed to explore the relationships between structural networks, exercise dependence, and depression.</div></div><div><h3>Results</h3><div>The findings revealed that the gray matter volume (GMV) and internal structural connectivity of the salience network were significantly increased in the group with exercise dependence symptoms. These changes were primarily associated with three key characteristics of exercise dependence: tolerance, conflict, and time commitment. Importantly, depression was found to mediate the relationship between the salience network and exercise dependence.</div></div><div><h3>Conclusions</h3><div>In older adults, increased structural connectivity within the salience network may amplify impulsive and reward-driven cravings for exercise and the ability to perceive emotional states such as depression. These findings indicate that the salience network could serve as a potential target for preventing and treating exercise dependence in the elderly population.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111770"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149225","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":"LncRNA Dleu2 regulates fear extinction memory through Celf2-driven synaptic plasticity","authors":"Ziwei Pi ,&nbsp;Jiazhi Jiang ,&nbsp;Lixin Dong ,&nbsp;Ziyue Xu ,&nbsp;Yi Zhang ,&nbsp;Gaomeng Luo ,&nbsp;Junhui Liu ,&nbsp;Runming Liu ,&nbsp;Zhehao Li ,&nbsp;Sha Liu ,&nbsp;Jincao Chen ,&nbsp;Wei Wei ,&nbsp;Xiang Li","doi":"10.1016/j.brainresbull.2026.111757","DOIUrl":"10.1016/j.brainresbull.2026.111757","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) are diverse regulators that shape many aspects of brain function. Nonetheless, their role in the mechanisms underlying fear extinction memory remains insufficiently explored. We profiled lncRNAs following the RNA capture-seq in the infralimbic prefrontal cortex (ILPFC) and identified the processed-transcript lncRNA deleted in lymphocytic leukemia-2 (Dleu2). The knockdown of Dleu2 by antisense oligonucleotide (ASO) impaired extinction memory, which demonstrated an essential role of Dleu2 in this process. To elucidate the underlying mechanism, CHIRP-seq and ATAC-seq analyses demonstrated an increased binding of Dleu2 within the intronic region of <em>Celf2</em>, accompanied by enhanced chromatin accessibility. This modulation subsequently promotes the transcription of <em>Celf2</em>, a critical gene involved in synaptic plasticity. Functionally, <em>Celf2</em> knockdown in ILPFC recapitulated the fear extinction memory deficit and reduced the number of dendritic spines. Together, these results indicate that lncRNA Dleu2 may serve as a potential therapeutic entry point for memory-related disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111757"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096062","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":"Functional magnetic resonance-based analysis of dynamic functional connectivity in patients with olfactory impairment in Parkinson's disease","authors":"Fangling He ,&nbsp;Huihua Liu","doi":"10.1016/j.brainresbull.2026.111750","DOIUrl":"10.1016/j.brainresbull.2026.111750","url":null,"abstract":"<div><h3>Objective</h3><div>The purpose of this research is to utilize resting-state functional magnetic resonance imaging (rs-fMRI), combined with sliding-window and cluster analysis methods. To identify alterations in functional connectivity (FC) patterns in patients with Parkinson's disease who exhibit olfactory dysfunction prior to the onset of motor symptoms, compared to healthy individuals.This method is intended to improve capabilities for the early detection of PD.</div></div><div><h3>Materials and Methods</h3><div>We recruited fifteen individuals from three distinct groups: PD patients with no or mild olfactory dysfunction (PD-N/MH), those with severe olfactory dysfunction, and healthy controls (HC). We gathered and analyzed resting-state fMRI data to examine dynamic FC across these groups, subsequently conducting a thorough statistical evaluation.</div></div><div><h3>Results</h3><div>Our cluster analysis identified two unique states of brain network connections across the groups. Notably, the subgroup with PD exhibited a more frequent occurrence and extended duration in state 1, along with reduced state transitions. Notably, the severity of olfactory dysfunction was significantly correlated with increased durations and frequencies in state 1 (<em>P</em> ＜0.05).</div></div><div><h3>Conclusion</h3><div>These observations underscore the significant relationship between state 1 connectivity patterns and olfactory impairment in PD patients. The discovery that PD patients with Parkinson’s disease (PD) “linger” in the sparsely connected state 1 provides a dynamic functional correlate of the progressive pathology that initially affects olfaction. Dynamic functional connectivity analysis successfully distinguished PD patients from healthy controls even prior to the onset of motor symptoms, suggesting its potential as a neuroimaging biomarker for Parkinson's disease. Consequently, this method may facilitate early identification, timely intervention, and improved clinical management of PD by providing an early warning signal before motor symptom——based diagnosis, thereby potentially delaying disease progression and alleviating the burden on patients, families, and society.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111750"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112424","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}