Brain Research最新文献

{"title":"Exploring the neurotoxic effects of microbial metabolites: A potential link between p-Cresol and autism spectrum disorders?","authors":"Mahi Basra ,&nbsp;Lauren Miceli ,&nbsp;Vatsala Mundra ,&nbsp;Alison Stern-Harbutte ,&nbsp;Hemangi Patel ,&nbsp;Jenifer Haynes ,&nbsp;Mayur S. Parmar","doi":"10.1016/j.brainres.2024.149427","DOIUrl":"10.1016/j.brainres.2024.149427","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex etiology, including genetic and environmental factors. A growing body of evidence (preclinical and clinical studies) implicates a potential role of gut microbiome dysregulation in ASD pathophysiology. This review focuses on the microbial metabolite p-Cresol, produced by certain gut bacteria such as <em>Clostridium</em>, and its potential role in ASD. The review summarizes studies investigating the gut microbiome composition in ASD patients, particularly the increased abundance of <em>Clostridium</em> species and associated gastrointestinal symptoms. The potential neurotoxic effects of p-Cresol are explored, including its influence on neurotransmitter metabolism (especially dopamine), neuroinflammation, and brain development. The mechanistic findings from the preclinical studies of p-Cresol’s induction of ASD-like behaviors and its impact on the dopaminergic system are discussed. Literature studies indicated increased levels of p-Cresol in the urine of patients with ASD. This increasing evidence suggests that p-Cresol may serve as a crucial biomarker for understanding the relationship between gut microbiota and ASD, opening avenues for potential diagnostic and therapeutic interventions.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149427"},"PeriodicalIF":2.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892034","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":"Mitochondrial fatty acid oxidase CPT1A ameliorates postoperative cognitive dysfunction by regulating astrocyte ferroptosis","authors":"Yinglan Su ,&nbsp;Qian Yuan","doi":"10.1016/j.brainres.2024.149424","DOIUrl":"10.1016/j.brainres.2024.149424","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a significant surgery-related complication marked by cognitive decline. Studies indicated that neuroinflammation, ferroptosis, and mitochondrial fatty acid metabolism might play parts in POCD, and might be mediated by Carnitine palmitoyl transferase 1a (CPT1A), but requires further investigations. Therefore, this study aims to investigate the mechanism of mitochondrial fatty acid oxidase CPT1A on mitochondrial function, ferroptosis, and inflammation in POCD pathogenesis.</div></div><div><h3>Methods</h3><div>SVG P12 astrocytes were used to investigate CPT1A’s control over mitochondrial function, ferroptosis, and inflammation affecting neurons. CPT1A was overexpressed using shRNA, with or without oligomycin to modulate mitochondrial function. Co-culture of these astrocytes with neurons, under similar conditions, assessed CPT1A’s impact on neuron damage via ferroptosis and inflammation. Gene and protein expressions of CPT1A, SYN, PSD95 were measured via RT-PCR and WB. Detection of JC-1, mitochondrial oxygen consumption rate (OCR), ROS, Fe²⁺ concentration, MOD, SOD and GSH/GSSG using kits was conducted to explore mitochondrial function and ferroptosis. Inflammation was quantified by ELISA for IL-6, IL-1β, and TGF-β.</div></div><div><h3>Results</h3><div>We successfully established CPT1A overexpression and knockdown models in astrocytes, confirming CPT1A’s ability to enhance mitochondrial membrane potential. Elevated CPT1A levels led to improved mitochondrial function, synaptic integrity, reduced oxidative stress, maintained iron homeostasis, and attenuated neuroinflammation, as reflected by increased SYN, PSD95, OCR, GSH and SOD, decreased ROS,GSSG, MDA, iron levels, and lowered inflammatory factors expression. Treatment with oligomycin reversed these protective effects, demonstrating the dependency of CPT1A’s benefits on intact mitochondrial respiration. In co-culture experiments with hippocampal neurons, astrocytes with manipulated CPT1A levels, particularly those co-treated with oligomycin, exacerbated neuronal mitochondrial dysfunction, oxidative stress, iron accumulation, and inflammation.</div></div><div><h3>Conclusion</h3><div>Overexpression of mitochondrial fatty acid oxidase CPT1A might improve synaptic integrity and rescue POCD by ameliorating astrocyte ferroptosis and neuroinflammation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149424"},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892035","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":"Tau, amyloid, iron, oligodendrocytes ferroptosis, and inflammaging in the hippocampal formation of aged rats submitted to an aerobic exercise program","authors":"R.C. Gutierre ,&nbsp;P.R. Rocha ,&nbsp;A.L. Graciani ,&nbsp;A.A. Coppi ,&nbsp;R.M. Arida","doi":"10.1016/j.brainres.2024.149419","DOIUrl":"10.1016/j.brainres.2024.149419","url":null,"abstract":"<div><div>Alzheimer’s disease is a progressive neurodegenerative disease affecting memory, language, and thinking with no curative treatment. Symptoms appear gradually, and pathological brain changes may occur twenty years before the physical and psychological signs, pointing to the urgent development of preventive interventions. Physical activity has been investigated as a preventive tool to defeat the main biological features of AD: pathological amyloid protein plaques, tau tangles, myelin degeneration, and iron deposits in the brain. This work quantifies tau tangles, amyloid, iron, and ferroptosis in oligodendrocytes in the aged rat hippocampal formation and statistically correlates neuron-neuron, neuron-glia, and glia-glia crosstalk and the effect of physical exercise on it. Our results indicate that iron overload in the oligodendrocytes is an inducer of ferroptosis; physical exercise reduces inflammaging, and improves axon-myelin volume relations; tau, amyloid, iron, and hippocampal formation cells present statistical correlations. Our data suggest the beneficial effects of physical exercise in AD and a mathematical relationship between the hippocampal formation cells in sedentary and active individuals, which should be considered in human and animal studies as a guide to a better understanding of crosstalk physiology.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149419"},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892044","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":"Mechanistic insights into Quetiapine’s Protective effects on cognitive function and synaptic plasticity in epileptic rats","authors":"Yanping Lan ,&nbsp;Ao Li ,&nbsp;Chenzhe Ding ,&nbsp;Jianxue Xia ,&nbsp;Xuebing Zhang ,&nbsp;Dongyang Luo","doi":"10.1016/j.brainres.2024.149426","DOIUrl":"10.1016/j.brainres.2024.149426","url":null,"abstract":"<div><div>The study aimed to examine the effects of Quetiapine, an atypical antipsychotic medication with purported neuroprotective qualities, on cognitive function and synaptic plasticity in epileptic rats. This investigation also sought to elucidate the mechanisms by which quetiapine influences the activity of the cyclic adenylate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and metallomatrix proteinase-9 (MMP9) expression in the context of epilepsy. The epileptic model was induced in rats through the administration of pilocarpine, with normal rats serving as the control group. Within the epilepsy group, two subgroups were established: one receiving normal saline and the other receiving quetiapine. Behavioral assays were utilized to assess learning, memory, and spatial exploration abilities. Furthermore, Western blot analysis, immunohistochemistry (IHC), and immunofluorescence (IF) staining were employed to evaluate the activity of the CREB/BDNF pathway, expression of MMP9 protein, and levels of synaptic plasticity-related proteins. Our study revealed that Quetiapine administration led to a notable enhancement in learning and memory in epileptic rats, as indicated by heightened drinking durations and visitation rates in behavioral assessments. Furthermore, Quetiapine upregulated the expression of pro-BDNF, m-BDNF, p-CREB, and CREB within the hippocampus, along with elevating mRNA levels of BDNF and CREB. Additionally, Quetiapine suppressed MMP-9 expression and promoted synaptic plasticity by augmenting SYN and PSD-95 expression levels in the hippocampus. Therefore, Quetiapine improved cognitive functions such as learning, memory, and spatial exploration in epileptic rats. Moreover, Quetiapine activated the CREB/BDNF signaling pathway, suppressed MMP-9 expression, and promoted synaptic plasticity.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149426"},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892047","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 multi-parametric MRI study on changes in the structure, function, and connectivity of thalamic subregions and their relationship with cognitive impairment in patients with subcortical ischemic vascular disease","authors":"Jing Huang ,&nbsp;Wenwen Wang ,&nbsp;Runtian Cheng ,&nbsp;Xiaoshuang Liu ,&nbsp;Li Chen ,&nbsp;Tianyou Luo","doi":"10.1016/j.brainres.2024.149420","DOIUrl":"10.1016/j.brainres.2024.149420","url":null,"abstract":"<div><h3>Introduction</h3><div>Prior researches have reported abnormal changes of thalamus in patients with subcortical ischemic vascular disease (SIVD), which was usually analyzed as a whole. However, it was currently unclear whether the structure, function and connectivity of thalamic subregions were differentially affected by this disease and affected different cognitive functions.</div></div><div><h3>Methods</h3><div>This study recruited 30 SIVD patients with cognitive impairment (SIVD-CI), 30 SIVD patients with cognitive unimpaired (SIVD-CU) and 32 normal controls. Then we compared the volume, local brain activity, structural connectivity and functional connectivity (FC) of thalamic subregions among three groups using multi-parameter MRI images. Finally, this study analyzed the relationship between these significant values and cognitive performance.</div></div><div><h3>Results</h3><div>In the SIVD-CI group, the weakened FC between temporal thalamus and frontal cortex, as well as the enhanced FC between temporal thalamus and motor cortex, were significantly correlated with executive impairment; the weakened structural connectivity between the thalamic subregions (pre-frontal thalamus, temporal thalamus and pre-motor thalamus) and the temporal and frontal cortices were significantly related to the declined auditory and working memory (<em>P</em> &lt; 0.05). Moreover, patients in the SIVD-CU group showed no abnormalities in FC, but exhibited a similar pattern of structural connectivity injury to the SIVD-CI group, which was relatively severer. Unexpectedly, there were no significant differences in the volume and local brain activity of all thalamic subregions among the three groups.</div></div><div><h3>Conclusions</h3><div>The functional and structural connectivity damages between the specific thalamic subregions and the specific cortices were correlated with the specific cognitive impairment in SIVD patients.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149420"},"PeriodicalIF":2.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892028","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":"Carboxylated Zn-phthalocyanine attenuates brain Aβ in AD model mouse","authors":"Ruochen Wang ,&nbsp;Abul Kalam Azad ,&nbsp;Abdullah Md Sheikh ,&nbsp;Shatera Tabassum ,&nbsp;Yuchi Zhang ,&nbsp;Xiaojing Zhou ,&nbsp;Jubo Bhuiya ,&nbsp;Fatema Binte Abdullah ,&nbsp;Shozo Yano ,&nbsp;Takahisa Ikeue ,&nbsp;Atsushi Nagai","doi":"10.1016/j.brainres.2024.149422","DOIUrl":"10.1016/j.brainres.2024.149422","url":null,"abstract":"<div><div>The deposition of aggregated amyloid β (Aβ) is considered as a key factor for Alzheimer’s Disease (AD). Previously, we demonstrated that a carboxylated Zn-phthalocyanine (ZnPc) inhibits Aβ fibril formation, consequently protects neurons in culture. This study evaluated the effects of ZnPc on pathological changes in an AD mouse model (J20). Nine-month-old J20 mice received weekly intraperitoneal injection of ZnPc (2 and 4 mg/kg) for 12 weeks. Cognitive performance was assessed using Y-maze and open field tests. ZnPc levels in the tissues were evaluated using near-infrared microscopy and spectroscopy. ZnPc accumulated primarily in the liver and kidney. A considerable amount was also detected in brain tissue, where it co-localized with neurons, microglia, and extracellularly deposited Aβ. ZnPc treatment (2 mg/kg) significantly improved cognitive functions of J20 mice. Immunostaining results showed that Aβ was positive intracellularly in neurons, and extracellularly around the vessels and parenchyma in the cortex and hippocampus of PBS-treated J20 mice, which was significantly decreased in ZnPc-treated J20 mice in a dose-dependent manner. Nissl staining demonstrated that neuronal numbers were increased both in the cortex and hippocampus. GFAP-positive astrocytes and Iba-1 positive microglia were decreased by ZnPc treatment. Also, vessel numbers were increased in ZnPc-treated groups. In PBS-treated group, aquaporin 4 immunopositive area extended beyond STL-positive vessels into the parenchyma, which was confined primarily around the vessels in the ZnPc-treated group. Claudin 5 levels were increased in ZnPc-treated group. Therefore, ZnPc can decrease brain Aβ deposition in J20 mice, suggesting it as a potential therapeutic agent for AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149422"},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892030","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":"Decoding thoughts, encoding ethics: A narrative review of the BCI-AI revolution","authors":"Thorsten Rudroff","doi":"10.1016/j.brainres.2024.149423","DOIUrl":"10.1016/j.brainres.2024.149423","url":null,"abstract":"<div><h3>Objectives</h3><div>This narrative review aims to analyze mechanisms underlying Brain-Computer Interface (BCI) and Artificial Intelligence (AI) integration, evaluate recent advances in signal acquisition and processing techniques, and assess AI-enhanced neural decoding strategies. The review identifies critical research gaps and examines emerging solutions across multiple domains of BCI-AI integration.</div></div><div><h3>Methods</h3><div>A narrative review was conducted using major biomedical and scientific databases including PubMed, Web of Science, IEEE Xplore, and Scopus (2014–2024). Literature was analyzed to identify key developments in BCI-AI integration, with particular emphasis on recent advances (2019–2024). The review process involved thematic analysis of selected publications focusing on practical applications, technical innovations, and emerging challenges.</div></div><div><h3>Results</h3><div>Recent advances demonstrate significant improvements in BCI-AI systems: 1) High-density electrode arrays achieve spatial resolution up to 5 mm, with stable recordings over 15 months; 2) Deep learning decoders show 40 % improvement in information transfer rates compared to traditional methods; 3) Adaptive algorithms maintain &gt;90 % success rates in motor control tasks over 200-day periods without recalibration; 4) Novel closed-loop optimization frameworks reduce user training time by 55 % while improving accuracy. Latest developments in flexible neural interfaces and self-supervised learning approaches show promise in addressing long-term stability and cross-user generalization challenges.</div></div><div><h3>Conclusions</h3><div>BCI-AI integration shows remarkable progress in improving signal quality, decoding accuracy, and user adaptation. While challenges remain in long-term stability and user training, advances in adaptive algorithms and feedback mechanisms demonstrate the technology’s growing viability for clinical applications. Recent innovations in electrode technology, AI architectures, and closed-loop systems, combined with emerging standardization frameworks, suggest accelerating progress toward widespread therapeutic use and human augmentation applications.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149423"},"PeriodicalIF":2.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifespan trajectories of the morphology and tractography of the corpus callosum: A 5.0 T MRI study","authors":"Xiaohui Chen ,&nbsp;Xitong Liu ,&nbsp;Xiaoli Zhong ,&nbsp;Jinxia Ren ,&nbsp;Huan Wang ,&nbsp;Xiaopeng Song ,&nbsp;Chenhong Fan ,&nbsp;Jia Xu ,&nbsp;Chunyu Li ,&nbsp;Liang Wang ,&nbsp;Qiang Hu ,&nbsp;Jinfeng Lv ,&nbsp;Yaowen Xing ,&nbsp;Lei Gao ,&nbsp;Haibo Xu","doi":"10.1016/j.brainres.2024.149413","DOIUrl":"10.1016/j.brainres.2024.149413","url":null,"abstract":"<div><div>The corpus callosum (CC) is the largest white matter fiber bundle connecting the two hemispheres, facilitating interhemispheric integration and hemispheric specialization. Neuroimaging studies have identified the CC as a marker for aging and various neuropsychiatric disorders. However, studies focusing on high-resolution imaging and detailed lifespan characterizations of CC morphology and connectivity are still limited, highlighting the need for further investigation.Utilizing the high-resolution brain imaging capabilities of 5.0 T ultra-high-field MRI, we collected lifespan data from 266 healthy adults aged 18–89. We segmented and measured the midsagittal area, circularity, thickness, and tractography of the CC using both linear regression and nonlinear fitting models. Our analysis revealed that, despite regional variations, these measures generally exhibited a brief initial increase, likely reflecting developmental maturation, followed by a rapid decline associated with aging-related degeneration. Coupling analysis further indicated that the positive correlation between CC morphology and tractography becomes stronger with increasing age, suggesting age-related structural-functional coupling. External validation and correlation with cognitive-behavioral tests showed that CC subregions with significant age-related changes predominantly involve areas connecting the frontal and parietal networks, particularly those associated with executive function and attentional control. These findings provide new insights into the lifespan evolution of CC morphology and tractography, as well as their degeneration associated with cognitive processing and sensory-motor integration.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149413"},"PeriodicalIF":2.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885113","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":"Dynamic analysis of frequency specificity in multilayer brain networks","authors":"Ming Ke ,&nbsp;Peihui Cao ,&nbsp;Xiaoliang Chai ,&nbsp;Xinyi Yao ,&nbsp;Guangyao Liu","doi":"10.1016/j.brainres.2024.149418","DOIUrl":"10.1016/j.brainres.2024.149418","url":null,"abstract":"<div><div>The brain is a highly complex and delicate system, and its internal neural processes are manifested as the interweaving and superposition of multi-frequency neural signals. However, traditional brain network studies are often limited to the whole frequency band or a specific frequency band, ignoring the potentially profound impact of the diversity of information within the frequency on the dynamics of brain networks. To comprehensively and deeply analyze this phenomenon, the present study is devoted to exploring the specific performance of brain networks at different frequencies. We used the maximum overlap discrete wavelet transform technique to finely divide the time series data into the following frequency bands: scale 1 (0.125–0.25 Hz), scale 2 (0.06–0.125 Hz), scale 3 (0.03–0.06 Hz) and scale 4 (0.015–0.03 Hz). Based on these frequency bands, we constructed multilayer networks from both dynamic and static perspectives, respectively. From the dynamic perspective, we quantitatively evaluated the dynamic differences among different frequency bands using metrics such as flexibility, promiscuity, integration, and recruitment, and found that scale 3 and scale 4 bands performed particularly well. In contrast, from a static perspective, we measured the cross-frequency interaction capability between different frequency bands through metrics such as multilayer clustering coefficient and entropy of multiplexing degree, and the results show that scale 2, scale 3, and scale 4 band networks have enhanced global integration capability and local capability. In addition, we explored the correlation of gender and age with the properties of brain networks in different frequency bands. In the scale 1 frequency band, the organization of brain functions showed significant gender differences, while in the scale 2 frequency band, there was a significant correlation between age and global efficiency. By integrating the dual perspectives of time and frequency domains, this study not only reveals the critical role of frequency specificity in the brain’s information processing and functional organization but also provides new perspectives for understanding the complex working mechanisms of the brain as well as gender- and age-related cognitive differences.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149418"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881164","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":"Titration of cuprizone induces reliable demyelination","authors":"Nicole Wigger,&nbsp;Johann Krüger,&nbsp;Elise Vankriekelsvenne,&nbsp;Markus Kipp","doi":"10.1016/j.brainres.2024.149410","DOIUrl":"10.1016/j.brainres.2024.149410","url":null,"abstract":"<div><div>Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cuprizone-induced demyelination, wherein mice are fed a diet containing the copper chelator cuprizone, is a well-established model that replicates key features of demyelination and remyelination. However, the dose–response relationship of cuprizone is complex; high concentrations can induce toxicity, whereas low doses may fail to produce reliable demyelination across subjects. This study aimed to investigate whether titration of the cuprizone concentration results in reliable acute demyelination and weight stabilization. To this end, experimental animals were intoxicated with cuprizone over a period of 5 weeks to induce acute demyelination. In one group, during the first 10 days, the initial cuprizone dose was gradually reduced until the experimental animals showed stable weights. Another group was subjected to a continuous cuprizone intoxication protocol without adaptions. Histological analyses were performed to quantify the extent of demyelination and glia activation. Animals of both groups experienced significant weight loss. Histological analyses revealed, despite adopting the cuprizone concentration, substantial demyelination of various brain regions, including the corpus callosum. This pattern was consistent across multiple staining methods, including anti-proteolipid protein (PLP), anti-myelin basic protein (MBP), and luxol-fast-blue (LFB) stains. Additionally, grey matter regions, specifically the neocortex, demonstrated significant demyelination. Accompanying these changes, there was notable activation and accumulation of microglia and astrocytes in white and grey matter regions. These histopathological changes were comparably pronounced in both cuprizone-treated groups. In summary, we demonstrate that titration of cuprizone is a reliable approach to induce acute demyelination in the mouse forebrain. This work represents a significant step toward refining animal models of MS, contributing to the broader effort of understanding and treating this complex disease.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149410"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}