Brain Research最新文献

{"title":"Dehydrocorybulbine blocks the Lyn-mediated MAPK pathway to promote anti-inflammatory polarization of microglia in mice after sevoflurane anesthesia","authors":"Biyu Zhang ,&nbsp;Weiqian Tian","doi":"10.1016/j.brainres.2026.150163","DOIUrl":"10.1016/j.brainres.2026.150163","url":null,"abstract":"<div><div>Dehydrocorybulbine (DHCB) has demonstrated efficacy in alleviating thermally induced acute pain. The present study sought to study the impact of DHCB on postoperative cognitive dysfunction (POCD). Mice or mouse BV2 cells were exposed to sevoflurane for modeling. Behavioral tests (Morris water maze, Y-maze, and novel object recognition test) and western blot analysis of APP, p-Tau (Thr231), and Tau protein expression in mouse hippocampal tissues were conducted to analyze cognitive impairment. DHCB inhibited M1 polarization of BV2 cells and mediated anti-inflammatory M2 polarization, further alleviating inflammatory damage. DHCB also alleviated cognitive impairment in mice dose-dependently by promoting the polarization of M1 to M2 microglia in the hippocampal CA1 region. DHCB targeted and inhibited the expression of Lck/Yes-related novel protein tyrosine kinase (Lyn) protein in microglia, thereby suppressing p38 MAPK signaling transduction. Reactivating Lyn reversed the above benefits of DHCB. Similarly, p38 MAPK signal inhibitor SB 202190 opposed the proinflammatory polarization of BV2 cells and inflammatory damage mediated by Lyn overexpression. In conclusion, our study demonstrates that DHCB inhibits Lyn expression in microglia, thereby suppressing p38 MAPK signal transduction and accelerating the polarization of microglia from M1 to M2 phenotype to alleviate sevoflurane-induced POCD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150163"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965132","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":"Daily temporal organization of inflammation and cognition-related factors and antioxidant enzymes are modified by an intracerebroventricular injection of amyloid-beta peptide (1–42) aggregates in the rat temporal cortex","authors":"Cinthia Coria-Lucero ,&nbsp;Mariana Lopez ,&nbsp;Sandra Gomez-Mejiba ,&nbsp;Dario Ramirez ,&nbsp;María Belén Delsouc ,&nbsp;Marilina Casais ,&nbsp;Richard Alba ,&nbsp;Jorge Leporatti ,&nbsp;Silvia Delgado ,&nbsp;Ana Cecilia Anzulovich ,&nbsp;Lorena Navigatore-Fonzo","doi":"10.1016/j.brainres.2025.150135","DOIUrl":"10.1016/j.brainres.2025.150135","url":null,"abstract":"<div><div>Alzheimer’s dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, oxidative damage, neuroinflammation, synaptic loss and neuronal cell death. The accumulation of Aβ in the brain plays a key role in the pathogenesis of AD. Elevated levels of Aβ causes an increase in oxidative damage and neuroinflammation both are considered key factors in the progression of AD. Also patients with Alzheimer’s show alterations in their circadian rhythms. Our objectives were (a) to analyze whether inflammation and cognition-related factors exhibit a day-night variation, (b) to verify whether antioxidant enzymes expression and activity exhibit a daily rhythm in the rat temporal cortex and (c) to evaluate the effects of an intracerebroventricular injection of Aβ-amyloid (1–42) aggregates on those temporal profiles. Four-month old males Holtzman rats were used in this study. Groups were defined as: 1) control 2) Aβ-injected. Rats were maintained under 12 h-Light:12 h-Dark conditions with food ad-libitum. Our results showed temporal patterns of nitrites, iNOS, catalase and glutathione peroxidase expression and activity, as well as Rc3 and Gap-43 mRNA, in the rat temporal cortex. An i.c.v. injection of Aβ abolishes the temporal pattern of Rc3 and Gap-43 mRNA. Also increased the rhythm’s mesor of NO and iNOS levels, reduced the mesor of CAT activity rhythms, and changed the phase of GPx activity patterns. These alterations in the temporal patterns of inflammation and redox status-related factors would affect cellular clock activity and consequently cognitive performance.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150135"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843530","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":"Ezetimibe mitigates microglial activation in Parkinson’s disease via TLR4/JNK pathway inhibition: evidence from network pharmacology and experimental validation","authors":"You-hai Hua ,&nbsp;Xin-yue Huang ,&nbsp;Jing-jing Ma ,&nbsp;Jin Wu ,&nbsp;Zeng-hui Zhou","doi":"10.1016/j.brainres.2025.150116","DOIUrl":"10.1016/j.brainres.2025.150116","url":null,"abstract":"<div><h3>Objective</h3><div>Neuroinflammation driven by microglial hyperactivation plays a critical role in Parkinson’s disease (PD). Ezetimibe, a cholesterol absorption inhibitor widely used for hyperlipidemia, has recently been implicated in neuroprotection. However, its impact on microglial activation in PD remains poorly understood. This study aimed to investigate the therapeutic potential and mechanisms of ezetimibe in modulating microglial activation in PD model.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to predict ezetimibe targets in PD, followed by validation in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Protein–protein interaction (PPI) analysis and Gene Ontology (GO) enrichment were used to identify relevant pathways. Molecular docking assessed ezetimibe-TLR4 binding. The effects of ezetimibe on pro-inflammatory mediator production, TLR4/JNK signaling, and microglia-induced dopaminergic neurotoxicity were evaluated using western blotting, qPCR, ELISA, and BV2–SH-SY5Y co-culture assays.</div></div><div><h3>Results</h3><div>Network pharmacology identified 53 common targets between ezetimibe and PD, with TLR4, TNF, and IL-1β as hub genes enriched in inflammatory processes. In BV2 cells, ezetimibe markedly reduced LPS-induced expression and secretion of iNOS, COX-2, Nitric oxide (NO), and IL-6 at both protein and transcriptional levels. Molecular docking revealed a strong binding affinity of ezetimibe to TLR4, although ezetimibe did not alter the basal expression of TLR4. Mechanistically, ezetimibe pretreatment suppressed LPS-induced JNK phosphorylation and AP-1 transcriptional activity, key downstream events of TLR4 activation. Consistently, pharmacological inhibition of TLR4 with TLR4-IN-C34 did not produce additional anti-inflammatory effects, confirming that ezetimibe acts through the TLR4 signaling pathway. Moreover, conditioned medium from ezetimibe-pretreated BV2 cells significantly reduced SH-SY5Y neuronal death, as indicated by decreased PI staining, LDH release, CCK8 assay, tyrosine hydroxylase (TH) protein levels and caspase-3 activation.</div></div><div><h3>Conclusion</h3><div>Ezetimibe suppresses microglial activation by targeting the TLR4/JNK pathway, thereby alleviating dopaminergic neuronal death. These findings highlight ezetimibe as a promising candidate for repurposing in PD therapy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150116"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789795","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":"Functional connectivity and graphical topological properties of the visual cortical network of minimally conscious state (MCS) patients","authors":"Zina Li ,&nbsp;Jichan Nian ,&nbsp;Shuiyan Li ,&nbsp;Zhiqing Deng ,&nbsp;Hang Wu ,&nbsp;Haili Zhong ,&nbsp;Xiyan Huang ,&nbsp;Pengmin Qin ,&nbsp;Jinhui Wang ,&nbsp;Qiuyou Xie ,&nbsp;Juan Chen","doi":"10.1016/j.brainres.2025.150122","DOIUrl":"10.1016/j.brainres.2025.150122","url":null,"abstract":"<div><div>The Minimally Conscious State (MCS) is a condition in which a patient, following a brain injury, exhibits minimal yet definite behavioral evidence of awareness, representing a crucial transitional state between unconsciousness and the full emergence of consciousness. Assessing preserved cognitive function, particularly visual function, is crucial for diagnosis and rehabilitation, given that vision is the primary source of sensory input. While MCS patients consistently exhibit visual behaviors, such as sustained fixation or pursuit eye movements, previous neuroimaging studies have treated the visual network as a monolith, leaving it unclear which part of their visual cortical neural networks is affected or preserved. Here, we investigated the visual neural network of patients, encompassing 38 visual cortical subregions, from the primary visual cortex (V1), which processes low-level features (e.g., contrast, orientation), to higher-level visual regions that mediate object recognition and visual attention. Threshold-free network-based statistical analysis revealed that inter-hemispheric connectivity is significantly decreased, while intra-hemispheric connectivity is largely preserved in the visual network of MCS patients. Graph-based analysis showed a longer characteristic path length in them, indicating impaired global integration. Nodal analysis revealed that the primary visual cortex (V1) is a more critical hub for information transfer, while the middle and high-level visual areas are less essential in MCS patients than in HCs. These findings provide a detailed characterization of the functional connectivity and topological properties of the visual cortical network in MCS patients, offering crucial insights for stimulus selection when using visual stimulation in rehabilitation and for assessing other cognitive functions.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150122"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808867","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":"Activation of PPARα by gemfibrozil lowers tau-associated neuropathology in the MAPT mouse model of Alzheimer’s disease","authors":"Moumita Majumder ,&nbsp;Debashis Dutta ,&nbsp;Ramesh K. Paidi ,&nbsp;Kalipada Pahan","doi":"10.1016/j.brainres.2025.150089","DOIUrl":"10.1016/j.brainres.2025.150089","url":null,"abstract":"<div><div>The current dogma states that inhibiting tau accumulation and its associated neuropathologies might be a relevant strategy to prevent neuronal loss and cognitive dysfunction in Alzheimer’s disease (AD). The present study demonstrates the therapeutic potential of an FDA-approved lipid lowering drug and an agonist of peroxisome proliferator and activated receptor α (PPARα), called gemfibrozil, in reducing tau accumulation and associated neuropathologies in the MAPT (PS19) mouse model of AD, expressing P301S mutated form of human tau protein in neurons. Daily oral treatment of gemfibrozil in MAPT mice reduced total tau and phosphorylated form of tau in the hippocampal subregions including CA1 and DG. Concurrently, gemfibrozil treatment upregulated PPARα level in the hippocampus and that was accompanied with inhibition of microgliosis and astrogliosis. Gemfibrozil also attenuated the loss of synaptic plasticity as determined by the expression of post-synaptic protein, PSD95, and calcium influx in the hippocampal tissue. The instrumental role of PPARα in gemfibrozil-mediated reduction of tauopathy was confirmed as PPARα deficiency in MAPT mice significantly augmented tau and phospho-tau accumulation in the hippocampus and gemfibrozil treatment failed to reverse tau pathology and gliosis in the brain of PPARα deficient MAPT mice. Lastly, gemfibrozil improved the cognitive function of MAPT mice during the symptomatic phase of disease progression, but it failed to reverse cognitive impairment in the PPARα deficient MAPT mice. These data suggest that neuroprotective effects of gemfibrozil in MAPT mice is mediated by PPARα. Moreover, targeting PPARα by small molecules like gemfibrozil may hold translational potential against tauopathy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150089"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713237","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":"Efficacy of transcranial direct current stimulation in children and adolescents with autism spectrum disorder: A systematic review and meta-analysis","authors":"Muhammad Maaz Amjad ,&nbsp;Hadiya Javed ,&nbsp;Muhammad Zuhaz Azeem ,&nbsp;Tuyyab Anwer ,&nbsp;Bilal Wazir Khan ,&nbsp;Muhammad Huzaifa Khattak ,&nbsp;Umer Zaryab Khan ,&nbsp;Muhammad Ahmed Zahoor ,&nbsp;Zobia Tabassum ,&nbsp;Muhammad Ehsan ,&nbsp;Hafiza Sidra ,&nbsp;Habeeb Ahmad ,&nbsp;Sarmad Nazir ,&nbsp;Komal Khan","doi":"10.1016/j.brainres.2025.150114","DOIUrl":"10.1016/j.brainres.2025.150114","url":null,"abstract":"<div><h3>Background</h3><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, repetitive behaviors, and loss of interests. Despite the use of conventional treatment such as medication and behavioral therapy, many children and adolescents still experience significant functional impairments. Recent advances in noninvasive brain stimulation have raised the interest of transcranial direct current stimulation (tDCS) in addressing core symptoms of ASD.</div></div><div><h3>Methods</h3><div>A comprehensive literature search of databases PubMed, Cochrane Library, and Google Scholar for relevant studies was conducted until March 28, 2025. A total of 1,443 records were identified. After duplicate removal and application of inclusion and exclusion criteria, 11 studies contributed to the Meta-analyses, while 28 studies were eligible for the systematic review.</div></div><div><h3>Results</h3><div>In addressing clinical outcomes, tDCS yielded significant improvement in social communication, the pooled data from 4 studies showed significant improvement in social communication (SMD =  − 0.66, 95 % CI [−0.94, −0.39] and p &lt; 0.00001), social awareness was also improved with tDCS (SMD = −0.60; 95 % CI [−1.12, −0.07] and p = 0.03) however, language skill showed no significant improvement (SMD = −0.11; 95 % CI [-0.44, 0.21] and p = 0.50). Moreover, tDCS also showed enhancement in restrictive repetitive behaviors (SMD = −0.60, 95 % CI [−0.85, −0.34] and p &lt; 0.00001). In addition, tDCS generated robust improvements in behavioral symptoms and regulations (SMD = −0.65; 95 % CI [−0.98, −0.32] and p &lt; 0.001). Finally, for overall symptom severity reduction in ASD by tDCS, assessed by SRS score, exhibited statistical improvements (SMD = −0.64; 95 % CI [−0.89, −0.39] and p &lt; 0.00001). However, the pooled analysis of 5 studies assessing ATEC score demonstrated no statistically significant difference (SMD = −0.61; 95 % CI [−1.34, 0.11] and p = 0.10) with high heterogeneity (p = 0.0006, I2 = 80 %). To overcome heterogeneity, we performed a sensitivity analysis, which made the result significant (SMD = −0.95; 95 % CI [−1.41, −0.49] and p &lt; 0.0001) with low heterogeneity (p = 0.16, I2 = 42 %).</div></div><div><h3>Conclusion</h3><div>tDCS appears to be a promising noninvasive therapy for improving social and behavioral symptoms of ASD. However, large-scale, multi-center RCTs with standardized protocols and longer follow-up durations are essential to determine optimal stimulation parameters and to identify which patients will benefit the most from it.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150114"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780217","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":"LRRN3 protects dopaminergic neurons by inhibiting glycolysis in Parkinson’s disease","authors":"Jinzhao Gao,&nbsp;Kunpeng Qin,&nbsp;Wenke Xian,&nbsp;Jiwen Ren,&nbsp;Anmu Xie,&nbsp;Binghui Hou","doi":"10.1016/j.brainres.2025.150119","DOIUrl":"10.1016/j.brainres.2025.150119","url":null,"abstract":"<div><div>Leucine-rich repeat neuronal protein 3 (LRRN3) is a multifunctional transmembrane protein with a crucial role in intracellular signal transduction. It is expressed at high levels in neurons. LRRN3 expression has been shown to be associated with Parkinson’s disease (PD) and aging. It is involved in regulating cellular energy metabolism. However, the specific mechanism involved remains undetermined. In this study, we investigated whether LRRN3 can regulate the expression of the key glycolytic enzymes HK2 and LDHA as well as lactate levels. We also studied the expression of the apoptosis-related regulatory factors Bax and Bcl-2 and the mitochondrial structure. We found that LRRN3 can inhibit the expression of HK2 and LDHA and reduce lactate levels in PD models. LRRN3 rescued apoptotic cells, reversed mitochondrial structure damage, and alleviated motor deficits in PD mice. When glycolysis was inhibited in mice treated with 2-deoxy-D-glucose, apoptosis, mitochondrial structure damage, and motor deficits were reversed. Mechanistically, LRRN3 targets and inhibits glycolytic enzymes to enhance lactate homeostasis, ultimately exerting a protective effect on dopaminergic (DA) neurons. Our data indicate that LRRN3 can protect DA neurons by suppressing glycolysis. It holds promise as a potential therapeutic target for PD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150119"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789794","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":"Neurodevelopmental origins of neurodegeneration: a lifespan perspective on brain vulnerability","authors":"Spandana Rajendra Kopalli ,&nbsp;Nasir Vadia ,&nbsp;Pooja Varma ,&nbsp;Swati Mishra ,&nbsp;Neha Joshi ,&nbsp;Pooja Bansal ,&nbsp;Shaker Al-Hasnaawei ,&nbsp;Ashish Singh Chauhan ,&nbsp;Hardik Jain ,&nbsp;Deepak Nathiya ,&nbsp;Anita Devi ,&nbsp;Hanish Singh Jayasingh Chellammal ,&nbsp;Priyanka Gupta ,&nbsp;Pranay Wal ,&nbsp;Sushruta Koppula","doi":"10.1016/j.brainres.2025.150134","DOIUrl":"10.1016/j.brainres.2025.150134","url":null,"abstract":"<div><div>Neurodegenerative disorders—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—are increasingly understood to have origins in early neurodevelopmental disturbances. This review examines how genetic, epigenetic, and environmental factors impact brain development during critical periods, predisposing individuals to neurodegeneration later in life. Prenatal and early-life exposures such as maternal stress, malnutrition, infection, and environmental toxins can alter key developmental processes, leading to long-term vulnerability. Mechanistic pathways linking early-life disruptions to neurodegenerative outcomes include persistent mitochondrial dysfunction, chronic neuroinflammation, increased oxidative stress, and aberrant synaptic pruning, all of which contribute to progressive neuronal damage and dysfunction. The gut-brain axis is also discussed as a key intermediary, where early microbiota dysbiosis alters neuroimmune signaling and inflammatory responses, modulating susceptibility to age-related neurological disorders. In this context, the review highlights emerging molecular and imaging biomarkers capable of detecting subtle neurodevelopmental deviations that may precede clinical symptoms by decades. The paper emphasizes the need for early-life interventions, including maternal nutritional optimization, management of prenatal stress, and microbiome-targeted strategies, as potential tools to reduce long-term neurological risk. Furthermore, it proposes the integration of precision medicine approaches aimed at individualized risk assessment and therapeutic targeting of developmental pathways. Adopting a lifespan perspective, this review argues for a paradigm shift from reactive to preventive strategies in neurology. Understanding the developmental roots of neurodegeneration opens new avenues for research and intervention, enabling resilience and reducing disease burden through early diagnostics and tailored therapeutics across the lifespan.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150134"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848897","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":"Molecular and neurochemical underpinnings of altered intrinsic neural timescales in Parkinson’s disease: a multimodal imaging and transcriptomics study","authors":"Zhi Wen ,&nbsp;Yuan-Zhi He ,&nbsp;Zhan-Xiang Hu ,&nbsp;Xin Huang ,&nbsp;Bao-jun Xie","doi":"10.1016/j.brainres.2025.150133","DOIUrl":"10.1016/j.brainres.2025.150133","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is characterized by widespread motor and non-motor impairments; however, the temporal dynamics underlying these functional disruptions remain unclear. The intrinsic neural timescale (INT), a novel neuroimaging metric that reflects the capacity of brain regions to integrate information over time, provides new insights into cortical hierarchy and dysfunction. In this study, we examined voxel-wise and network-level alterations in INT among PD patients using resting-state fMRI and integrated their molecular correlates with transcriptomic data from the Allen Human Brain Atlas and PET-derived neurotransmitter receptor maps. Our analysis revealed localized reductions in INT in the left insula, Rolandic operculum, and middle temporal gyrus in PD, while large-scale network hierarchies remained preserved. Partial least squares regression analysis indicated that changes in INT were significantly associated with spatial gene expression gradients, particularly those involving immune-metabolic stress and synaptic maintenance. Furthermore, cell-type enrichment analysis identified excitatory and inhibitory neurons as key cellular contributors. Notably, INT alterations correlated with cortical GABAA receptor density, suggesting a role for inhibitory neurotransmission in temporal integration deficits. These findings highlight a multiscale pathophysiological framework linking functional brain dynamics, molecular architecture, and neurochemical modulation in PD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150133"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833011","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":"Chronic dynamic behavioral changes and upregulation of glutamatergic signaling proteins following traumatic brain injury in females","authors":"Caiti-Erin Talty ,&nbsp;Susan F. Murphy ,&nbsp;Pamela J. VandeVord","doi":"10.1016/j.brainres.2025.150115","DOIUrl":"10.1016/j.brainres.2025.150115","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a leading cause of disability worldwide, with approximately 50 % of individuals with mild TBI experiencing persistent, debilitating symptoms. Clinical findings have demonstrated that females are more likely than males to develop chronic symptoms and tend to report greater symptom severity. Despite this, the pathophysiological mechanisms underlying these sex-specific chronic outcomes remain poorly understood. Using a clinically-relevant preclinical model of closed-head controlled impact in adult female rats, we examined affective-like behavior alterations up to twelve weeks post-injury. Injured animals exhibited early increases in risk-taking and disinhibition behaviors, followed by decreased social novelty preference and evidence of increased grooming behavior at eight weeks. Glutamatergic protein expression was measured in the frontal cortex and hippocampus at twelve weeks to assess glutamatergic alterations associated with chronic behavioral outcomes. TBI resulted in elevated expression of N-methyl-D-aspartate receptor subunits GluN1, GluN2A, and GluN2B, along with a decreased GluN2A:GluN2B ratio in the frontal cortex. Additionally, glutamate transporters GLT-1 and GLAST were upregulated in the hippocampus and frontal cortex, respectively. Together, these findings demonstrated that females exhibited dynamic behavioral changes accompanied by region-specific upregulation of glutamatergic signaling proteins. Further investigations are warranted to investigate circuit-level glutamatergic dysfunction and its potential role as a mechanistic driver of chronic TBI-related deficits in females.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150115"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789793","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}