Pub Date : 2024-12-25DOI: 10.1016/j.brainres.2024.149426
Yanping Lan , Ao Li , Chenzhe Ding , Jianxue Xia , Xuebing Zhang , Dongyang Luo
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.
{"title":"Mechanistic insights into Quetiapine’s Protective effects on cognitive function and synaptic plasticity in epileptic rats","authors":"Yanping Lan , Ao Li , Chenzhe Ding , Jianxue Xia , Xuebing Zhang , 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}
Pub Date : 2024-12-24DOI: 10.1016/j.brainres.2024.149420
Jing Huang , Wenwen Wang , Runtian Cheng , Xiaoshuang Liu , Li Chen , Tianyou Luo
Introduction
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.
Methods
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.
Results
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 (P < 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.
Conclusions
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.
{"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 , Wenwen Wang , Runtian Cheng , Xiaoshuang Liu , Li Chen , 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> < 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}
Pub Date : 2024-12-23DOI: 10.1016/j.brainres.2024.149422
Ruochen Wang , Abul Kalam Azad , Abdullah Md Sheikh , Shatera Tabassum , Yuchi Zhang , Xiaojing Zhou , Jubo Bhuiya , Fatema Binte Abdullah , Shozo Yano , Takahisa Ikeue , Atsushi Nagai
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.
{"title":"Carboxylated Zn-phthalocyanine attenuates brain Aβ in AD model mouse","authors":"Ruochen Wang , Abul Kalam Azad , Abdullah Md Sheikh , Shatera Tabassum , Yuchi Zhang , Xiaojing Zhou , Jubo Bhuiya , Fatema Binte Abdullah , Shozo Yano , Takahisa Ikeue , 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}
Pub Date : 2024-12-22DOI: 10.1016/j.brainres.2024.149423
Thorsten Rudroff
Objectives
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.
Methods
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.
Results
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 >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.
Conclusions
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.
目的：本文旨在分析脑机接口（BCI）和人工智能（AI）集成的机制，评估信号采集和处理技术的最新进展，并评估人工智能增强的神经解码策略。该综述确定了关键的研究差距，并研究了跨BCI-AI集成多个领域的新兴解决方案。方法：对PubMed、Web of Science、IEEE Xplore、Scopus等主要生物医学和科学数据库（2014-2024）进行叙述性回顾。对文献进行了分析，以确定BCI-AI集成的关键发展，特别强调了最近的进展（2019-2024）。审查过程涉及对选定出版物的专题分析，重点是实际应用、技术革新和新出现的挑战。结果：最近的进展表明，BCI-AI系统有了显著的改进：1)高密度电极阵列实现了高达5 mm的空间分辨率，稳定记录超过15 个月；2)与传统方法相比，深度学习解码器的信息传输率提高了40% %；3)自适应算法在不重新校准的情况下，在200天的时间内保持bbb90 %的运动控制任务成功率；4)新颖的闭环优化框架在提高准确率的同时，将用户训练时间缩短了55% %。灵活神经接口和自监督学习方法的最新发展显示出解决长期稳定性和跨用户泛化挑战的希望。结论：BCI-AI集成在提高信号质量、解码精度和用户适应性方面取得了显著进展。尽管在长期稳定性和用户培训方面仍然存在挑战，但自适应算法和反馈机制的进步表明，该技术在临床应用中的可行性越来越大。最近在电极技术、人工智能架构和闭环系统方面的创新，加上新兴的标准化框架，表明朝着广泛的治疗应用和人类增强应用加速进展。
{"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 >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}
Pub Date : 2024-12-22DOI: 10.1016/j.brainres.2024.149413
Xiaohui Chen , Xitong Liu , Xiaoli Zhong , Jinxia Ren , Huan Wang , Xiaopeng Song , Chenhong Fan , Jia Xu , Chunyu Li , Liang Wang , Qiang Hu , Jinfeng Lv , Yaowen Xing , Lei Gao , Haibo Xu
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.
{"title":"Lifespan trajectories of the morphology and tractography of the corpus callosum: A 5.0 T MRI study","authors":"Xiaohui Chen , Xitong Liu , Xiaoli Zhong , Jinxia Ren , Huan Wang , Xiaopeng Song , Chenhong Fan , Jia Xu , Chunyu Li , Liang Wang , Qiang Hu , Jinfeng Lv , Yaowen Xing , Lei Gao , 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}
Pub Date : 2024-12-21DOI: 10.1016/j.brainres.2024.149418
Ming Ke , Peihui Cao , Xiaoliang Chai , Xinyi Yao , Guangyao Liu
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.
{"title":"Dynamic analysis of frequency specificity in multilayer brain networks","authors":"Ming Ke , Peihui Cao , Xiaoliang Chai , Xinyi Yao , 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}
Pub Date : 2024-12-21DOI: 10.1016/j.brainres.2024.149410
Nicole Wigger, Johann Krüger, Elise Vankriekelsvenne, Markus Kipp
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.
{"title":"Titration of cuprizone induces reliable demyelination","authors":"Nicole Wigger, Johann Krüger, Elise Vankriekelsvenne, 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}
Pub Date : 2024-12-20DOI: 10.1016/j.brainres.2024.149421
Adriana Souza dos Santos , Meirylanne Gomes da Costa , Wellington de Almeida , Gabrielle Batista de Aguiar , Anna Luísa Lothhammer Bohn , Ana Paula Rodrigues Martini , Andrey Vinicios Soares Carvalho , Thiago Ângelo Smaniotto , Alessandra Schmitt Rieder , Ana Paula Muterle Varelad , Thais Fumaco Teixeirad , Paulo Michel Roehe , Angela Terezinha de Souza Wyse , Carla Dalmaz , Carlos Alexandre Netto , Lenir Orlandi Pereira
Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections. The aim of this study was to evaluate the long-term impacts on cognitive and memory functions, as well as neuroinflammatory and glial alterations in the hippocampus, in offspring of both sexes exposed to a model of congenital Zika virus infection. Pregnant rats were subcutaneously inoculated with ZIKV-BR at a dose of 1 × 10^7 plaque-forming units (PFU mL^-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). From postnatal day 70, the animals underwent behavioral tests. On postnatal day 80, the animals were euthanized, and hippocampal samples were collected for biochemical and histological analyses. In the open field test, females displayed more exploratory behavior and less grooming, while no significant differences in locomotion were observed between the sexes. Additionally, ZIKV-exposed females showed a reduction in grooming behavior compared to ZIKV-exposed males. In the memory test, males in the ZIKV group exhibited greater memory impairment, spending more time to locate the correct quadrant, while females showed relatively better performance. Neuroinflammatory markers, such as TNF-α, were significantly elevated in the hippocampus of ZIKV-exposed animals, regardless of sex. However, microglial and astrocytic responses, indicated by higher IBA1 and GFAP density, were only observed in male ZIKV rats. In conclusion, our findings suggest that congenital ZIKV exposure leads to sex-specific behavioral and neuroinflammatory alterations. While both males and females exhibited some behavioral changes, males were more significantly impacted in memory performance. Additionally, increased neuroinflammatory markers and glial activation were observed in the hippocampus of ZIKV-exposed animals, with a pronounced response in males. These results highlight the long-term impact of ZIKV infection on neurodevelopment, emphasizing the importance of considering sex differences in studies of congenital ZIKV syndrome.
{"title":"Long-term impact of congenital Zika virus infection on the rat hippocampus: Neuroinflammatory, glial alterations and sex-specific effects","authors":"Adriana Souza dos Santos , Meirylanne Gomes da Costa , Wellington de Almeida , Gabrielle Batista de Aguiar , Anna Luísa Lothhammer Bohn , Ana Paula Rodrigues Martini , Andrey Vinicios Soares Carvalho , Thiago Ângelo Smaniotto , Alessandra Schmitt Rieder , Ana Paula Muterle Varelad , Thais Fumaco Teixeirad , Paulo Michel Roehe , Angela Terezinha de Souza Wyse , Carla Dalmaz , Carlos Alexandre Netto , Lenir Orlandi Pereira","doi":"10.1016/j.brainres.2024.149421","DOIUrl":"10.1016/j.brainres.2024.149421","url":null,"abstract":"<div><div>Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections. The aim of this study was to evaluate the long-term impacts on cognitive and memory functions, as well as neuroinflammatory and glial alterations in the hippocampus, in offspring of both sexes exposed to a model of congenital Zika virus infection. Pregnant rats were subcutaneously inoculated with ZIKV-BR at a dose of 1 × 10^7 plaque-forming units (PFU mL^-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). From postnatal day 70, the animals underwent behavioral tests. On postnatal day 80, the animals were euthanized, and hippocampal samples were collected for biochemical and histological analyses. In the open field test, females displayed more exploratory behavior and less grooming, while no significant differences in locomotion were observed between the sexes. Additionally, ZIKV-exposed females showed a reduction in grooming behavior compared to ZIKV-exposed males. In the memory test, males in the ZIKV group exhibited greater memory impairment, spending more time to locate the correct quadrant, while females showed relatively better performance. Neuroinflammatory markers, such as TNF-α, were significantly elevated in the hippocampus of ZIKV-exposed animals, regardless of sex. However, microglial and astrocytic responses, indicated by higher IBA1 and GFAP density, were only observed in male ZIKV rats. In conclusion, our findings suggest that congenital ZIKV exposure leads to sex-specific behavioral and neuroinflammatory alterations. While both males and females exhibited some behavioral changes, males were more significantly impacted in memory performance. Additionally, increased neuroinflammatory markers and glial activation were observed in the hippocampus of ZIKV-exposed animals, with a pronounced response in males. These results highlight the long-term impact of ZIKV infection on neurodevelopment, emphasizing the importance of considering sex differences in studies of congenital ZIKV syndrome.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149421"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876167","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}
Pub Date : 2024-12-20DOI: 10.1016/j.brainres.2024.149417
Manuel Ramírez-Sánchez , Isabel Prieto , Ana Belén Segarra , Inmaculada Banegas , Magdalena Martínez-Cañamero , Germán Domínguez-Vías , Raquel Durán , Francisco Vives
The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M−B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging. The tested ages were: fetuses, rats of one week, one month, five month and two year old. In homogenate, the results demonstrate high levels of positive correlations (left versus right homogenate) with high levels of significance, without differences among the ages analyzed. In synaptosomes the results demonstrate positive correlations with a level close to statistical significance (left versus right synaptosomes) in fetuses, significant correlations at one week, one month and five months, particularly at one week and five months, and a radical decrease in the level of left versus right correlation between synaptosomes of two-year-old animals, which could suggest a functional loss of the bilateral synaptic interaction that could be carried out at earlier ages by M−B ArgAP activity. The interaction between left or right synaptosomes versus left or right homogenates demonstrate decreasing levels of positive correlation from fetuses to five month old rats, without differences between correlations of the left synaptosomes with correlations of the right ones. However, in two year old rats the values of correlations of the left synaptosomes diverged significantly from the right ones. While left synaptosomal correlations exhibited positive values, the right correlations exhibited negative ones, showing. a clear asymmetry between both sides in aged rats suggesting a marked reduction with aging of the synaptic function in the right hemisphere.
{"title":"Asymmetric intra and inter-hemispheric subcellular rat brain correlation of arginyl-aminopeptidase activity during development and aging","authors":"Manuel Ramírez-Sánchez , Isabel Prieto , Ana Belén Segarra , Inmaculada Banegas , Magdalena Martínez-Cañamero , Germán Domínguez-Vías , Raquel Durán , Francisco Vives","doi":"10.1016/j.brainres.2024.149417","DOIUrl":"10.1016/j.brainres.2024.149417","url":null,"abstract":"<div><div>The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M−B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging. The tested ages were: fetuses, rats of one week, one month, five month and two year old. In homogenate, the results demonstrate high levels of positive correlations (left versus right homogenate) with high levels of significance, without differences among the ages analyzed. In synaptosomes the results demonstrate positive correlations with a level close to statistical significance (left versus right synaptosomes) in fetuses, significant correlations at one week, one month and five months, particularly at one week and five months, and a radical decrease in the level of left versus right correlation between synaptosomes of two-year-old animals, which could suggest a functional loss of the bilateral synaptic interaction that could be carried out at earlier ages by M−B ArgAP activity. The interaction between left or right synaptosomes versus left or right homogenates demonstrate decreasing levels of positive correlation from fetuses to five month old rats, without differences between correlations of the left synaptosomes with correlations of the right ones. However, in two year old rats the values of correlations of the left synaptosomes diverged significantly from the right ones. While left synaptosomal correlations exhibited positive values, the right correlations exhibited negative ones, showing. a clear asymmetry between both sides in aged rats suggesting a marked reduction with aging of the synaptic function in the right hemisphere.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149417"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876119","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}
Pub Date : 2024-12-20DOI: 10.1016/j.brainres.2024.149416
Qin Yang , Tingting Chen , Shaofa Li , Chengmin Yang , Xingwu Zheng , Sanying Mao , Ning Liu , Shenglong Mo , Dengxing Li , Meiling Yang , Zhicheng Lu , Lina Tang , Xiaorui Huang , Xia Liu , Chongdong Jian , Yixia Yin , Jingwei Shang
This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer’s disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis. Additionally, alterations were observed in the expression levels of cellular autophagy-related proteins (LC3-II, P62), which were reversed by treatment with autophagic inhibitor 3-methyladenine (3-MA). Furthermore, the expression of mitochondrial autophagy-related proteins PINK1 and Parkin was affected, with 3-MA alleviating this effect. In summary, our study elucidates the complex interplay among cognitive decline, increased Aβ deposition, and mitochondrial dysfunction in the AD + CCH model, and suggests that modulating autophagy could be a potential therapeutic strategy for treating the AD + CCH model.
{"title":"Inhibition of autophagy attenuates cognitive decline and mitochondrial dysfunction in an Alzheimer’s disease mouse model with chronic cerebral hypoperfusion","authors":"Qin Yang , Tingting Chen , Shaofa Li , Chengmin Yang , Xingwu Zheng , Sanying Mao , Ning Liu , Shenglong Mo , Dengxing Li , Meiling Yang , Zhicheng Lu , Lina Tang , Xiaorui Huang , Xia Liu , Chongdong Jian , Yixia Yin , Jingwei Shang","doi":"10.1016/j.brainres.2024.149416","DOIUrl":"10.1016/j.brainres.2024.149416","url":null,"abstract":"<div><div>This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer’s disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis. Additionally, alterations were observed in the expression levels of cellular autophagy-related proteins (LC3-II, P62), which were reversed by treatment with autophagic inhibitor 3-methyladenine (3-MA). Furthermore, the expression of mitochondrial autophagy-related proteins PINK1 and Parkin was affected, with 3-MA alleviating this effect. In summary, our study elucidates the complex interplay among cognitive decline, increased Aβ deposition, and mitochondrial dysfunction in the AD + CCH model, and suggests that modulating autophagy could be a potential therapeutic strategy for treating the AD + CCH model.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149416"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876125","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号