Journal of Neuroscience Research最新文献

{"title":"Impact of Age and Prior History of Ethanol Exposure on Ethanol-Induced Patterns of Neuronal Activation in cFos-LacZ Adolescent Male and Female Rats","authors":"Harper J. Coleman,&nbsp;Devon T. Applegate,&nbsp;Kimberly M. Papastrat,&nbsp;Trevor T. Towner,&nbsp;Elena I. Varlinskaya,&nbsp;David F. Werner","doi":"10.1002/jnr.70163","DOIUrl":"10.1002/jnr.70163","url":null,"abstract":"<div>\u0000 \u0000 <p>Adolescent binge alcohol alters late-developing brain regions and increases the risk for long-term reward, cognitive, and emotional dysregulation. Adolescent intermittent ethanol (AIE) exposure in rodents produces similar behavioral alterations into adulthood, but the effects of acute high-dose ethanol on patterns of neuronal activation in late developing brain regions remain poorly understood. In the current study, adolescent male and female cFos-LacZ rats were acutely challenged with water or 4 g/kg ethanol intragastrically (IG) on postnatal day (P) 25 or P45, early- and late-adolescence, with brains collected 1 h later. P45 rats with a history of water or AIE (10 exposures every other day from P25 to P45) were included as a chronic exposure condition. β-galactosidase expression was used as a proxy for Fos neuronal activation. Acute IG gavage increased neuronal activation in multiple brain regions irrespective of water or ethanol challenge, and increases were attenuated by adolescent chronic exposure. Increased neuronal activation was evident only in the central amygdala (CeA) after acute ethanol challenge, with this effect being attenuated by AIE. Functional network mapping revealed age-, sex-, and exposure-related differences: water-exposed adolescent males had salient network hub regions, while control females had age-related transitions from salient to executive control network regions. Ethanol disrupted these trajectories. In males, acute ethanol reduced functional network connectivity, with chronic ethanol decentralizing hubs. In females, ethanol enhanced connectivity centered on the nucleus accumbens. These findings highlight the CeA as an ethanol-sensitive region across sexes, but reveal sex differences in adolescent ethanol exposure on functional networks.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167465","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":"Sex-Dependent Alterations in Behavioral Development of Mice Lacking α5-Nicotinic Acetylcholine Receptors","authors":"Danai Papavranoussi Daponte,&nbsp;Filippos Marinos,&nbsp;Eleni Matala,&nbsp;Irini Skaliora","doi":"10.1002/jnr.70156","DOIUrl":"https://doi.org/10.1002/jnr.70156","url":null,"abstract":"<p>Complex neurodevelopmental disorders such as autism spectrum disorders (ASD) and schizophrenia are characterized by impaired social interactions, cognitive deficits, and repetitive behaviors. Genome-wide association studies (GWAS) have identified the α5 nicotinic acetylcholine receptor (α5-nAChR) subunit as a significant risk factor for these neuropsychiatric conditions. The α5 subunit is a critical modulator of neural circuit dynamics, specifically through its functional involvement within vasoactive intestinal peptide (VIP)-positive interneurons; however, its role in the sex-dependent maturation of behavioral phenotypes remains poorly understood. We characterized α5-nAChR knockout (ACNA5) mice to investigate the neurodevelopmental consequences of α5 subunit loss. ACNA5 mice displayed sexually dimorphic and age-dependent core symptoms relevant to ASD and schizophrenia. Regarding anxiety-like behavior, there was an opposite sex pattern between genotypes, evident only in adulthood. Cognitive assessment using the novel object location task revealed early-onset spatial memory deficits in ACNA5 females, whereas males exhibited a progressive decline from adolescence to adulthood. In the social domain, adult ACNA5 mice failed to exhibit social novelty preference; females displayed complete social indifference, while males displayed a pronounced familiarity bias. In addition, ACNA5 mice of both sexes displayed amplified repetitive behavior, emerging earlier in males, and poor nest-building scores across developmental stages. Together, these findings identify the α5-nAChR subunit as a crucial modulator of the maturation of neural circuits underlying social motivation, cognition, and emotional regulation. Our results implicate α5-containing nicotinic receptors in the pathogenesis of neurodevelopmental disorders and establish the ACNA5 mouse as a valuable model for investigating sex-specific developmental trajectories and therapeutic windows.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Pharmacological Targeting of Hsp72 Overexpression/Induction in an Alzheimer's Disease Mouse Model With Combined Amyloid and Tau Pathology","authors":"J. P. S. Marshall,&nbsp;A. Harutyunyan,&nbsp;J. Ng,&nbsp;O. M. West,&nbsp;J. M. Collins,&nbsp;A. E. King,&nbsp;J. Morizzi,&nbsp;P. Wright,&nbsp;A. C. Calkin,&nbsp;B. G. Drew,&nbsp;N. C. Jones,&nbsp;P. A. Adlard,&nbsp;M. A. Febbraio,&nbsp;D. C. Henstridge","doi":"10.1002/jnr.70161","DOIUrl":"https://doi.org/10.1002/jnr.70161","url":null,"abstract":"<p>Heat shock protein 72 (Hsp72), a stress-inducible member of the Hsp70 family, has been implicated in mitigating the pathogenic effects of amyloid-beta (Aβ) and tau pathology; both key factors associated with the development and progression of Alzheimer's disease (AD). However, no in vivo study has been conducted to investigate the ability of Hsp72 to provide benefit when both Aβ and tau pathology are present concurrently. This study set out to utilize a genetic approach (transgenic overexpression) and a pharmacological validation approach (BGP-15) to increase Hsp72 expression in mice exhibiting Aβ and tau pathology (5xFADxTg30 model). Our findings indicate that genetic Hsp72 overexpression did not significantly alter Aβ or tau burden, deficits in motor performance, or alterations to body composition in this model, but modestly improved survival rates (driven by findings in male mice) and altered anxiety-like behavior (driven by findings in female mice). Similarly, BGP-15 treatment was unable to rescue behavioral traits, motor deficits, body composition, or alleviate Aβ or tau accumulation, although this treatment also showed a trend towards enhancing survival (again in male mice) and altered anxiety-like behavior (specifically in female mice). While the 5xFADxTg30 mice demonstrated seizure susceptibility compared to WT mice, BGP-15 was unable to alleviate this trait. These findings were independent of any measurable increase in Hsp72 abundance in the brain in response to BGP-15. Together, these findings suggest a limited impact of genetic overexpression and pharmacological targeting of Hsp72 protein abundance in this combined Aβ and tau model, although some sex-specific differences are noted.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treadmill Training Improves Functional Recovery After Injection of Adipose-Derived Stromal Vascular Fraction in Rats With a Spinal Cord Injury","authors":"Céline Ertlen,&nbsp;Maxime Bonnet,&nbsp;Mostafa Seblani,&nbsp;Thelma Coyle,&nbsp;Jean-Michel Brezun,&nbsp;Nicolas Serratrice,&nbsp;Patrick Decherchi,&nbsp;Tanguy Marqueste","doi":"10.1002/jnr.70158","DOIUrl":"10.1002/jnr.70158","url":null,"abstract":"<p>Spinal cord injuries (SCI) are a major health concern, resulting in substantial functional deficits, including motor and sensory impairments around and below the affected area. Despite continuous efforts, current spinal cord repair strategies have shown limited therapeutic success. The adipose-derived stromal vascular fraction (SVF) is a heterogeneous cell population with trophic, angiogenic, and immunomodulatory properties that has previously been shown to improve functional recovery after experimental SCI. The present study investigated whether treadmill rehabilitation could enhance the therapeutic effects of autologous SVF transplantation following severe thoracic SCI. Thirty-six male Sprague Dawley rats were divided into four groups: NaCl (sodium chloride) (spinal cord contusion with NaCl injection), SVF (contusion with SVF autograft), NaCl-T (contusion with NaCl injection and treadmill training), and SVF-T (contusion with SVF autograft and treadmill training). Behavioral recovery was assessed weekly over 12 weeks using the BBB locomotor score and ladder climbing test, while gait and electrophysiological analyses were performed at the study endpoint. The combined treatment produced greater improvements in locomotor performance than either SVF transplantation or treadmill training alone, as demonstrated by higher BBB and ladder climbing scores together with improved gait parameters. Electrophysiological analyses further showed that SVF treatment restored rate-dependent depression of the H-reflex, reflecting improved spinal sensorimotor inhibitory function. Collectively, these findings demonstrate that treadmill rehabilitation potentiates the functional benefits of autologous SVF transplantation and supports the combination of cell therapy and rehabilitation as a promising strategy to enhance functional recovery after traumatic SCI.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intraplantar CFA Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes","authors":"Caitlin E. Fenech,&nbsp;Neda Assareh,&nbsp;Karin R. Aubrey","doi":"10.1002/jnr.70157","DOIUrl":"https://doi.org/10.1002/jnr.70157","url":null,"abstract":"<p>In humans, chronic pain is characterized by a combination of heightened nociceptive sensitivity along with emotional comorbidities, with more women impacted than men. A reported limitation of preclinical models is that they often fail to encapsulate this complexity, and few studies have directly compared behavioral outcomes between male and female mice. The intraplantar Complete Freund's adjuvant (CFA) inflammatory pain model is a widely used preclinical model of persistent mechanical and thermal hypersensitivity, which triggers sex-dependent adaptations in neuronal signaling. However, the literature regarding the duration of pain hypersensitivity and the presence or absence of associated locomotor and anxiety-like changes is inconsistent. Therefore, this study aimed to systematically assess the CFA model's capacity to duplicate pain comorbidities in male and female mice. CFA-injected or saline control male and female mice were assessed over 3 weeks for mechanical and cold nociceptive sensitivity (von Frey and acetone test), locomotion (open field test), and anxiety-like behaviors (light–dark and elevated plus maze tests). CFA-injected mice of both sexes reliably developed mechanical hypersensitivity and cold allodynia. Transient locomotor deficits were observed only in male mice at early timepoints, and no changes in anxiety-like behaviors in either males or females were observed. Hence, the CFA persistent pain model is a practical tool for inducing pronociceptive states in male and female mice but does not reliably produce anxiety-like comorbidities over the tested time periods, suggesting that additional factors may be necessary to elicit these behavioral outcomes.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Cognitive and Affective Outcomes Following Bilateral 6-Hydroxydopamine Lesions of the Substance Nigra or Striatum in Rats","authors":"Bianca Andretto de Mattos,&nbsp;Elaine Del Bel,&nbsp;Humberto Milani,&nbsp;Rúbia Maria Weffort de Oliveira,&nbsp;Jéssica Mendes Bonato","doi":"10.1002/jnr.70154","DOIUrl":"10.1002/jnr.70154","url":null,"abstract":"<p>The majority of animal models of Parkinson's disease (PD) focus on motor symptoms that are induced by unilateral injections of such neurotoxins as 6-hydroxydopamine (6-OHDA) in nigrostriatal dopaminergic pathways. However, motor changes that are induced by unilateral 6-OHDA injections may interfere with the identification of cognitive and affective dysfunctions induced by dopaminergic neurodegeneration. To select an appropriate method for studying nonmotor symptoms of PD and potential neuroprotective treatments, the present study compared behavioral effects of bilateral 6-OHDA infusions directly in the substantia nigra pars compacta (SNpc) or striatum in rats. A battery of behavioral tests, including affective and cognitive tasks, was performed for 22 days after 6-OHDA nigrostriatal lesions. The massive degeneration of tyrosine hydroxylase-immunoreactive neurons was observed in the SNpc, striatum, and ventral tegmental area with 6-OHDA infusions in either the SNpc or striatum. Concerning functional outcomes, 6-OHDA infusions in the striatum decreased general exploratory activity 7 days after the lesion. Rats that received 6-OHDA in the SNpc exhibited cognitive impairments and despair-like behavior. A decrease in the number of newborn neurons was found in the hippocampus in rats that received 6-OHDA in the striatum, indicating a alteration of neuron maturation. 6-OHDA infusions in both the SNpc and striatum impacted the maturation of newborn hippocampal neurons. These results indicate that bilateral injections of 6-OHDA in the SNpc might be useful for studying nonmotor symptoms of PD.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Generation of Functional Oligodendrocytes From Human Induced Pluripotent Stem Cells Through Small Molecule Guided Differentiation","authors":"Isabella Bienjonetti,&nbsp;Vincent Roy,&nbsp;Marie-Josée Beaudet,&nbsp;Aurélie Louit,&nbsp;Laurie Martineau,&nbsp;François Berthod,&nbsp;Nicolas Dupré,&nbsp;François Gros-Louis","doi":"10.1002/jnr.70155","DOIUrl":"10.1002/jnr.70155","url":null,"abstract":"<div>\u0000 \u0000 <p>Oligodendrocytes (OLs) are essential for central nervous system (CNS) function through their role in axon myelination, and their dysfunction is implicated in a range of neurological disorders. Despite this, in vitro modeling of human OL biology remains limited by the scarcity of primary human OLs. Furthermore, while induced pluripotent stem cells (iPSCs) offer a promising source of human OLs, current differentiation protocols remain complex, inefficient, and time-consuming. Here, we present an optimized protocol to generate OLs from iPSCs (iOLs) using defined soluble factors supplemented in the culture media. Within 28 days, cultures yielded an average of 85% O4⁺ iOLs, and by Day 38, approximately 70% expressed MBP, a key marker of mature OLs. Bulk RNA-seq analysis confirmed a stepwise transcriptional progression consistent with OL lineage identity, with upregulation of key OL-specific transcripts and gene expression profiles. Comparative transcriptomic analyses further revealed increased expression of gene networks associated with myelination, extracellular matrix remodeling, and gliogenesis when iOLs were cultured on aligned nanofiber scaffolds. Importantly, iOLs formed compact myelin sheaths around axons and showed enhanced maturation in a three-dimensional (3D) environment, highlighting the importance of spatial and matrix-derived cues in OL development. This study establishes a cost- and time-efficient approach for generating functional OLs from iPSCs, with broad applicability for disease modeling, drug screening, and the development of regenerative therapies.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900731","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":"Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function","authors":"James Melrose","doi":"10.1002/jnr.70151","DOIUrl":"10.1002/jnr.70151","url":null,"abstract":"<p>This narrative review examines the essential roles of heparan sulfate proteoglycans (HSPGs) in brain development, synaptic function, axonal guidance, synapse formation and stabilization, and the establishment of correctly interconnected neural networks. Distinct HSPG profiles help shape precise neural circuits, whereas HSPG dysregulation is associated with impaired neurodevelopmental processes, cognitive decline, and pathological changes in brain tissues. These findings emphasize the importance of HSPGs in normal brain function and in disease-associated tissue dysfunction. HSPGs are a diverse group of proteins with critical roles in the CNS and PNS, including synaptic function, neurodevelopment, neurodegeneration, cell migration, and regulation of neuroprogenitor stem cell niches in the subventricular ependymal zone and subgranular dentate gyrus. Together, the diverse functions of HSPGs place them as master regulators of tissue form and function in health and disease.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resting-State Brain Entropy Reveals Altered Neural Dynamics and Cognitive Associations in Mild Traumatic Brain Injury: A Longitudinal Study","authors":"Li Jiang,&nbsp;Ze Wang,&nbsp;Steven Roys,&nbsp;Rosy Linda Njonkou Tchoquessi,&nbsp;Prashant Raghavan,&nbsp;Neeraj Badjatia,&nbsp;Rao P. Gullapalli,&nbsp;Jiachen Zhuo","doi":"10.1002/jnr.70153","DOIUrl":"https://doi.org/10.1002/jnr.70153","url":null,"abstract":"<p>Mild traumatic brain injury (mTBI) is associated with persistent physical, cognitive, and emotional symptoms, yet the functional brain changes that accompany recovery remain incompletely understood. This longitudinal study investigated brain entropy (BEN), a resting-state measure of irregularity or complexity of spontaneous BOLD activity derived from resting-state functional magnetic resonance imaging (rs-fMRI), during the first year following mTBI. Data of rs-fMRI were acquired from 48 patients with mTBI at the acute (&lt; 14 days), 6-month, and 12-month post-injury visits, and 34 healthy controls (HCs). BEN was quantified using sample entropy. Patients with mTBI also underwent behavioral assessments evaluating quality of life and cognitive function. Behavioral assessments demonstrated progressive improvements in patient-reported quality of life and objective cognitive performance. Cross-sectional analyses revealed dynamic, time-dependent alterations in BEN. Compared with HCs, patients with mTBI exhibited higher BEN in precuneus, temporal, occipital, and sensorimotor regions during the acute and 6-month stages, whereas lower BEN was observed in sensorimotor, occipital, and frontoparietal regions at the 12-month follow-up. Longitudinal analyses demonstrated progressive regional reductions in BEN over time. Several associations between longitudinal changes in regional BEN and cognitive performance were nominally significant, particularly in the precuneus, but none survived multiple comparison corrections. These findings indicate that mTBI recovery is accompanied by dynamic, regionally specific changes in resting state BOLD irregularity. BEN may therefore provide a promising imaging biomarker for tracking the evolving neural dynamics underlying recovery following mTBI.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Cognitive and Structural Correlates of Pain Extent and Central Sensitization Symptoms in Older Women and Men With Chronic Pain","authors":"Keiko Yamada,&nbsp;Hiroki Tabata,&nbsp;Kaito Takabayashi,&nbsp;Hitoshi Naito,&nbsp;Hideyoshi Kaga,&nbsp;Koji Kamagata,&nbsp;Yoshifumi Tamura","doi":"10.1002/jnr.70152","DOIUrl":"https://doi.org/10.1002/jnr.70152","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic pain in later life may be accompanied by alterations in brain structure and cognition, but whether pain extent and central sensitization symptoms identify distinct brain-behavior patterns remains unclear. We examined associations of pain extent and central sensitization symptoms, assessed using the 9-item Central Sensitization Inventory (CSI-9), with regional gray matter volume and cognitive function in community-dwelling older adults. This cross-sectional study included 272 participants with chronic pain from the Bunkyo Health Study. Participants were classified as having single-site or multisite pain and by CSI-9 score as having lower or higher scores, with ≥ 12 defining the higher group. Regional gray matter volume was quantified using 0.3-Tesla magnetic resonance imaging, and cognition was assessed using the Trail Making Test Part B (TMT-B), processing speed, and global and domain-specific measures. Pain extent and CSI-9 group interacted for TMT-B performance, with the longest completion time in participants with single-site pain and a higher CSI-9 score. No other cognitive outcome remained significant after correction for multiple testing. In categorical analyses, the higher CSI-9 group had smaller volumes in the right middle frontal gyrus, bilateral anterior cingulate cortex, right insula, right hippocampus, and bilateral amygdala, whereas pain extent and the interaction were not associated with regional volume. In a contextual comparison, only the single-site/higher CSI-9 group showed slower TMT-B performance than participants with no current pain. Pain extent and central sensitization symptoms may represent partly distinct dimensions of chronic pain, although the small single-site/higher CSI-9 group and attenuation in several sensitivity analyses warrant caution.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807711","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}