Journal of integrative neuroscience最新文献

{"title":"Lipid Ratio Biomarkers as Protective Factors for Depressive Symptoms in Newly Diagnosed Metabolic Syndrome: Evidence From Regression Modeling.","authors":"Spas Kitov, Tanya Deneva, Maria-Florance Kitova, Lyudmila Kitova, Kristina Stoyanova, Iliana Petrova, Drozdstoy Stoyanov","doi":"10.31083/JIN49628","DOIUrl":"https://doi.org/10.31083/JIN49628","url":null,"abstract":"<p><strong>Background: </strong>Obesity and depression have a bidirectional relationship. Previous work has shown that obesity increases the risk of depression, while atypical depression can elevate the risk of obesity. This study aimed to investigate the associations between anthropometric markers, lipid and insulin resistance biomarkers, inflammatory cytokines, and adipokines with depressive symptom severity in individuals with newly diagnosed metabolic syndrome (MetS).</p><p><strong>Methods: </strong>88 treatment-naïve adults with newly identified MetS, without known coronary artery disease, were included. Clinical assessments comprised anthropometric measures, while laboratory analyses measured lipid metabolism markers, insulin resistance indicators, inflammatory cytokines, and adipokines. Depressive symptom severity was assessed using the von Zerssen Depression Scale (DS), validated for the Bulgarian population. To explore latent structures within biomarker domains, principal component analyses (PCA) were performed. Associations between depressive symptoms and biomarkers were then examined in two steps: first, using linear regression with PCA-derived component scores, and second, through hierarchical multiple regression focusing on selected individual biomarkers, controlling for covariates such as age and gender.</p><p><strong>Results: </strong>PCA identified distinct latent structures within anthropometric, lipid, insulin resistance, and cytokine domains, though regression analyses using PCA-derived component scores did not yield significant associations with depressive symptoms (all <i>p</i> > 0.050). Hierarchical multiple regression with selected biomarkers showed that lower low-density lipoprotein cholesterol (LDLc)/Apolipoprotein B (ApoB) ratios were consistently associated with higher depressive symptom severity (Model 1: β = -0.332, <i>p</i> = 0.011; Model 2: β = -0.326, <i>p</i> = 0.012; Model 3: β = -0.319, <i>p</i> = 0.013), while higher interleukin-6 (IL-6) levels were independently linked to greater symptom severity (Model 1: β = 0.217, <i>p</i> = 0.052; Model 3: β = 0.230, <i>p</i> = 0.033). ApoB/apolipoprotein A1 (ApoA1) ratios and age showed weaker or non-significant effects.</p><p><strong>Conclusions: </strong>LDLc/ApoB ratio and IL-6 levels are independently associated with depressive symptom severity in newly diagnosed MetS, highlighting their potential as clinically relevant biomarkers. These findings highlight perspectives for integrating lipid and inflammatory profiles in the assessment of depression risk within MetS populations.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"49628"},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773986","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":"Astrocytes and Their Role in the Development and Progression of Alzheimer's Disease: Gatekeepers of Neurodegeneration.","authors":"Irena Svobodova, Zdenka Bendova, Jiri Novotny","doi":"10.31083/JIN49765","DOIUrl":"https://doi.org/10.31083/JIN49765","url":null,"abstract":"<p><p>Astrocytes are increasingly recognized as central players in the pathogenesis of Alzheimer's disease (AD), exhibiting both neuroprotective and neurotoxic functions, which complicates their role in disease progression. Under physiological conditions, astrocytes support neuronal homeostasis, facilitate synaptic function, and promote the clearance of Amyloid-β (Aβ), thereby contributing to neuroprotection. In the context of AD, however, reactive astrocytes can adopt detrimental phenotypes, releasing pro-inflammatory cytokines, generating oxidative stress, and disrupting neuronal networks, thereby exacerbating neurodegeneration. Consequently, the shift from a protective to a neurotoxic phenotype may not only drive neuronal loss but also accelerate AD progression. The dual roles of astrocytes and the dynamic changes in their functions-protecting neurons under normal conditions while promoting pathology when dysregulated-underscore their complex contribution to AD pathophysiology. Elucidating the mechanisms underlying astrocyte-mediated neuroprotection and neurotoxicity is essential for developing targeted therapeutic strategies aimed at modulating astrocyte activity to slow or prevent disease progression. This review aims to present and critically discuss recent advances and ongoing controversies concerning the involvement of astrocytes in AD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"49765"},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773927","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":"Regional Associations Between Ocular Vascular Parameters and Enlarged Perivascular Spaces in the Basal Ganglia and Centrum Semiovale.","authors":"Nuo Ma, Juan Tao, Qiong Dong, Qiuyue Yu, Haichao Wang, Ping Li, Quan Yuan, Aiping Jin, Peng Gao, Li Gong","doi":"10.31083/JIN49070","DOIUrl":"https://doi.org/10.31083/JIN49070","url":null,"abstract":"<p><strong>Background: </strong>Enlarged perivascular spaces (EPVS) represent a hallmark imaging feature of cerebral small vessel disease. The ocular vasculature is an anatomical extension of cerebral vessels, constituting part of the microvascular system; however, the relationship between ocular vascular characteristics and EPVS remains poorly understood. In this study, we examined the association between ocular vascular parameters and the regional distribution of EPVS in patients with minor stroke.</p><p><strong>Methods: </strong>Patients diagnosed with minor stroke between 2021 and 2024 were prospectively enrolled. Ocular vascular characteristics were assessed using optical coherence tomography angiography (OCTA) and ophthalmic arterial ultrasound (OAU), while 3.0 T magnetic resonance imaging (MRI) was performed to evaluate EPVS in the centrum semiovale (CSO) and basal ganglia (BG). Demographic characteristics, clinical risk factors, neuroimaging findings, and laboratory data were recorded at admission.</p><p><strong>Results: </strong>A total of 111 participants were enrolled, with a mean age of 65.23 ± 7.62 years; 43.24% were female. At baseline, 43 patients (38.74%) had high CSO-EPVS burden, and 61 (54.95%) had high BG-EPVS burden. In multivariate regression analysis, superficial retinal capillary plexus perifoveal density (odds ratio [OR] = 0.87, <i>p</i> = 0.020) measured by OCTA and diabetes mellitus were independently associated with BG-EPVS, whereas the resistive index of the ophthalmic artery (OR = 1.33, <i>p</i> < 0.001) measured by OAU was independently and positively associated with CSO-EPVS.</p><p><strong>Conclusions: </strong>Ocular microvascular density was associated with BG-EPVS, whereas ocular vascular elasticity was associated with CSO-EPVS. These findings support the hypothesis that these EPVS subtypes arise from distinct vascular mechanisms - microvascular hypoperfusion versus reduced vascular elasticity.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"49070"},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774030","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":"Atractylodin Suppresses Fibrotic Scar Formation and Enhances Functional Recovery Following Spinal Cord Injury.","authors":"Zhenwei Li, Chao Fang, Chengcheng Feng, Zuomeng Wu, Chenhao Zhao, Cailiang Shen","doi":"10.31083/JIN47565","DOIUrl":"https://doi.org/10.31083/JIN47565","url":null,"abstract":"<p><strong>Background: </strong>Fibrous scar formation significantly inhibits axonal regeneration and functional recovery following spinal cord injury (SCI). Atractylodin (ATD), an active constituent of traditional Chinese medicine, exhibits broad pharmacological properties, including anti-inflammatory and anti-fibrotic effects. Nevertheless, the potential therapeutic role of ATD in SCI and its underlying molecular mechanisms remain to be fully elucidated.</p><p><strong>Methods: </strong>An SCI model was established in C57 mice. Motor function was assessed using the Basso Mouse Scale scoring system, inclined plane test, swimming test, and footprint analysis. Immunohistochemical staining was performed to evaluate fibrotic scar formation and neuronal survival. Western blotting and quantitative real-time PCR (qPCR) were also employed to investigate the molecular mechanisms underlying ATD-mediated regulation of fibroblasts following SCI.</p><p><strong>Results: </strong>ATD administration significantly enhanced motor function in SCI mice, reduced the area of fibrotic scars, and suppressed the expression of fibrotic markers. Mechanistically, ATD inhibited Mothers Against Decapentaplegic Homolog 2/3 (SMAD2/3) phosphorylation and nuclear translocation, thereby suppressing fibroblast activation and extracellular matrix deposition, while promoting neuronal survival and axonal regeneration.</p><p><strong>Conclusions: </strong>ATD mitigates fibrotic scar formation by targeting the Transforming Growth Factor Beta (TGF-β)/SMAD pathway, thereby facilitating axonal regeneration and functional recovery. This offers a promising therapeutic strategy for SCI.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"47565"},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773912","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 Alterations in the Cholinergic Neural Circuits of Patients With Alzheimer's Disease: A Donepezil Intervention Study Using Resting-State Functional Magnetic Resonance Imaging.","authors":"Yufei Guo, Zhenzhong Zhang, Bo Chen, Hao Liu, Fuquan Wei, Xiaozheng Liu, Zhongwei Guo","doi":"10.31083/JIN50039","DOIUrl":"https://doi.org/10.31083/JIN50039","url":null,"abstract":"<p><strong>Background: </strong>Although donepezil alleviates Alzheimer's disease (AD) symptoms by raising acetylcholine levels, its impact on cholinergic pathways remains unclear. In this longitudinal, resting-state functional magnetic resonance imaging (rs-fMRI) study, we investigated donepezil-induced changes in cholinergic pathway networks in AD.</p><p><strong>Methods: </strong>AD patients and healthy controls (HCs) were enrolled. AD patients received 24 weeks of donepezil treatment. Cognitive and emotional symptoms were assessed using the Mini-Mental State Examination (MMSE), Cornell Scale for Depression in Dementia (CSDD), and Neuropsychiatric Inventory (NPI) pre- and post-treatment. rs-fMRI was used to examine basal forebrain (BF) functional connectivity.</p><p><strong>Results: </strong>Sixteen AD patients and 16 HCs completed the study. Post-treatment MMSE scores improved, and NPI and CSDD scores decreased. Reduced BF functional connectivity in the left cerebellar lobule VI, post-treatment, was revealed by rs-fMRI. Compared with HCs, post-treatment AD patients showed lower BF functional connectivity in the right postcentral gyrus (PoG); pre-treatment patients exhibited higher BF functional connectivity in the left cerebellar lobule VI. Right PoG functional connectivity was negatively correlated with disease duration pre-treatment and positively correlated with MMSE post-treatment.</p><p><strong>Conclusions: </strong>Donepezil improved clinical symptoms in AD by modulating the BF-PoG cholinergic pathway.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"50039"},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773911","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 Lipid Metabolism in Alzheimer's Disease: Emerging Insights and Future Directions.","authors":"Jeyakumar Balakrishnan, Suganya Kannan, Kathiresan Shanmugam, Dhavamani Sugasini","doi":"10.31083/JIN48436","DOIUrl":"https://doi.org/10.31083/JIN48436","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that is conventionally characterized by amyloid-β and tau pathology. There is growing evidence, however, that lipid metabolic disturbances are part of the biology of the disease, and not a secondary phenomenon. Lipid signaling controls membrane organization, amyloid precursor protein, tau phosphorylation, mitochondrial energetics, neuroinflammatory signaling, and synaptic stability. The accumulating genetic evidence, including risk variants in the <i>APOE</i> (apolipoprotein E), <i>ABCA1</i> (ATP-binding cassette subfamily A member 1), <i>ABCA7</i> (ATP-binding cassette subfamily A member 7), and <i>TREM2</i> (Triggering receptor expressed on myeloid cells 2) genes, further makes lipid transport and lipid-sensing pathways central to late-onset AD vulnerability. Recent developments in lipidomics based on mass spectrometry have revealed concerted changes in phospholipids, sphingolipids, sterols, and oxidized lipid derivatives in brain tissue and peripheral biofluids. Instead of single abnormalities, directional metabolic imbalance is indicated by pathway changes, including decreased sphingomyelin-to-ceramide ratios and decreased polyunsaturated phospholipids. Co-analysis of lipidomic, genomic, and proteomic data has shown the existence of metabolically different subgroups, which aids genotype stratified risk evaluation and the lipid responder phenotype concept. Protein-centered therapies are complemented by therapeutic strategies that focus on lipid homeostasis, such as the regulation of cholesterol efflux, sphingolipid metabolism, pro-resolving lipid mediators, and metabolic reprogramming. There is also emerging evidence that implicates peroxisomal dysfunction and compromised glymphatic clearance in interfering with lipid balance. Although this field of research has come a long way, the issues of proving causality, standardizing lipidomic techniques, and converting pathway signatures into clinically useful resources persist. Restructuring AD as a lipid network instability disorder offers a systems level model of earlier diagnosis and targeted treatment.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"48436"},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774020","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 Role of Artificial Intelligence in Diagnosing Acute Ischemic Stroke Using Diffusion MRI: A Multicenter External Validation Study.","authors":"Beyza Nur Kuzan, Ali Abbasian Ardakani, Mahmut Esat Aykan, Mustafa Demir, Servan Yaşar, Mehmet Semih Çakır, Afshin Mohammadi, Taha Yusuf Kuzan","doi":"10.31083/JIN48811","DOIUrl":"https://doi.org/10.31083/JIN48811","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke is a time-sensitive medical emergency requiring rapid and accurate diagnosis to improve patient outcomes. While Diffusion-Weighted Imaging (DWI) on magnetic resonance imaging (MRI) is highly sensitive, artificial intelligence (AI) offers a potential solution to enhance diagnostic speed and accuracy. In this study we aimed to evaluate and externally validate a DWI-MRI-based deep learning model for automated stroke detection and compare its multicenter diagnostic performance with expert radiologists to determine generalizability and clinical utility.</p><p><strong>Methods: </strong>This retrospective study involved 732 patient cases (acute ischemic stroke and non-stroke controls) from three different centers. A deep convolutional neural network (CNN) model was developed, trained, and internally validated using data from center 1 (n = 452 for training, n = 80 for validation). The model's generalizability was then tested using independent external validation datasets from center 2 (n = 100) and center 3 (n = 100). The model's diagnostic performance (sensitivity, specificity, accuracy, and area under the receiver operating characteristic (ROC) curve (AUC)) was systematically compared with that of three expert radiologists.</p><p><strong>Results: </strong>The deep learning model demonstrated excellent diagnostic performance. In the internal validation, the model achieved 100% sensitivity, 100% specificity, and 100% accuracy (AUC = 1.000). Crucially, it maintained high performance on the external validation cohorts, achieving 100% sensitivity, 98% specificity, and 99% accuracy for both center 2 (AUC = 0.987) and center 3 (AUC = 0.986). This performance was comparable with the expert radiologists, who also achieved high accuracy across all datasets. Visualization techniques (gradient-weighted class activation map (Grad-CAM)) confirmed that the AI model focused on the correct pathological regions when making its classifications.</p><p><strong>Conclusions: </strong>The DWI-MRI-based deep learning model provides high and reliable diagnostic accuracy for acute ischemic stroke, with performance comparable with that of expert radiologists. Its robust performance across multicenter data highlights its potential as a dependable decision-support tool in emergency departments, especially in settings with limited specialist availability, to facilitate faster and more consistent stroke diagnoses.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"48811"},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774008","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":"Investigating Gender Differences in the Link Between Physical Activity and Depression in Middle-aged and Older Chinese Adults via Network Analysis and Simulation Study.","authors":"Ying Xiong, Yiguo Deng, Miao Yu, Qihan Zhang, Siyu Li, Jiaying Li, Zengjie Ye","doi":"10.31083/JIN47468","DOIUrl":"https://doi.org/10.31083/JIN47468","url":null,"abstract":"<p><strong>Background: </strong>Depression affects 28.4% of middle-aged and older adults globally, exacerbating functional decline, mortality, and healthcare burdens. Physical activity mitigates depression through neurobiological and psychosocial pathways, although efficacy varies significantly by gender. Current evidence lacks clarity regarding optimal physical activity intensity and interventions. This study aimed to identify the physical activity patterns most strongly associated with depression and to derive potential intervention targets for middle-aged and older Chinese adults.</p><p><strong>Methods: </strong>The data from 3739 participants in the 2020 China Health and Retirement Longitudinal Study were analyzed. Gaussian graphical models were adopted to recognize core and bridge symptoms within physical activity-depression networks across genders. Subsequently, computer-simulated interventions were conducted to determine the optimal targets for reducing depressive symptoms by gender.</p><p><strong>Results: </strong>Both male and female networks identified \"depressed\" as the central symptom. However, the bridge symptoms differed: males exhibited a bridge role for \"days with moderate physical activity per week\", whereas females showed this for \"duration of moderate physical activity per day\". Network comparison test revealed significant gender differences in edge weights (<i>p</i> = 0.007), with 14 edges being statistically significant. Simulation interventions consistently pinpointed \"depressed\" and \"stuck\" as effective targets for intervention across genders.</p><p><strong>Conclusions: </strong>Moderate physical activity most strongly correlated with depression. For men, interventions might prioritize increasing the regularity per week with moderate physical activity to prevent depression, whereas for women, focusing on the duration per day of such activity could be a promising target.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"47468"},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773929","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 Capacitance-Based System for Measuring Licking Behaviour in Rodents With Sub-Second Precision.","authors":"Yuliia Martynova, José Antonio González","doi":"10.31083/JIN49809","DOIUrl":"https://doi.org/10.31083/JIN49809","url":null,"abstract":"<p><strong>Background: </strong>The ability to measure drinking behaviour in laboratory animals is fundamental for neuroscience and metabolic research. In particular, the analysis of lick microstructure is an important tool for studying ingestive behaviour, motivation, and food preference. To capture lick microstructure, sensors capable of detecting licks in animals with a time resolution of only a few milliseconds are required.</p><p><strong>Methods: </strong>We designed a lick sensor that can be used with standard drinking bottles and does not require modifications to animal cages. It can be used in any experimental arena and with one or more drinking bottles simultaneously. Moreover, this lickometer reports lick events in real time and is thus suitable for driving additional laboratory hardware for real-time loop-control experiments. Our design is publicly available.</p><p><strong>Results: </strong>To validate our lick sensor we measured licks in mice offered water or sucrose drinks. Our sensor captured the same features of licking behaviour that have been reported before for these conditions using alternative lick sensors.</p><p><strong>Conclusions: </strong>The lick sensor described here is reliable while being easy to build and less expensive than known alternatives. It also facilitates the integration of lick measurements with other laboratory instruments in real time. This sensor lowers the barrier to implementing lick-sensing instrumentation in the laboratory which will be of benefit for research in neuroscience and metabolism.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"49809"},"PeriodicalIF":2.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773786","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":"Involvement of the Primary Auditory Cortex-Basolateral Amygdala Circuit in Altered Conditioned Fear Memory Retrieval Following Electromagnetic Field Exposure in Mice.","authors":"Zhilin Cui, Lei Shi, Meiying Yang, Chenxu Chang, Shunkang Jin, Yanhui Hao, Xuelong Zhao, Yanjie Lu, Yang Li, Hongyan Zuo","doi":"10.31083/JIN48640","DOIUrl":"https://doi.org/10.31083/JIN48640","url":null,"abstract":"<p><strong>Background: </strong>Electromagnetic field (EMF) exposure is increasingly common and has been implicated in a range of effects on human health. Conditioned fear memory plays a critical role in enabling organisms to respond appropriately to previously encountered threats. Despite growing interest in the neurobiological consequences of EMF exposure, its impact on the neural circuits underlying conditioned fear responses has not been clearly defined.</p><p><strong>Methods: </strong>Using a mouse model exposed to combined microwave and static magnetic fields, we examined the involvement of the primary auditory cortex-basolateral amygdala (Au1-BLA) circuit in EMF-associated alterations in conditioned fear retrieval. A multifaceted experimental approach was employed, including behavioral assays, viral tracing, genetically encoded calcium imaging, chemogenetic modulation, histopathological analysis, and immunofluorescence.</p><p><strong>Results: </strong>Exposure was associated with reduced conditioned fear memory retrieval, pathological changes in Au1 and BLA tissue ultra-structures, and decreased Nissl bodies in Au1 neurons and Au1-BLA neuronal fiber projections. The attenuation of conditioned fear memory retrieval coincided with decreased calcium activity in Au1 and BLA neurons. Consistently, chemogenetic activation of Au1 calcium-dependent protein kinase II (CaMKII)-expressing neurons enhanced calcium activity in BLA neurons during fear retrieval and was accompanied by changes in cholinergic signaling in the BLA. These findings suggest that cholinergic neuronal populations downstream of the Au1-BLA circuit are sensitive to EMF exposure and may participate in EMF-related modulation of fear retrieval.</p><p><strong>Conclusions: </strong>Our findings support an association between EMF exposure and altered conditioned fear expression involving functional changes within the Au1-BLA circuit, especially for the changes in calcium activity and chemogenetic modulation of Au1 CaMKII-expressing neurons. This study provides direct experimental evidence linking EMF exposure to circuit-level functional interactions underlying fear memory retrieval.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 4","pages":"48640"},"PeriodicalIF":2.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773953","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}