Pub Date : 2024-10-02DOI: 10.1016/j.brainres.2024.149258
Nicolas M. Brunet, Britney M. Aguirre
The face fusiform area (FFA) plays a pivotal role in face recognition, yet the precise timeline of its activity remains debated. Using EEG, we conducted three experiments to investigate how expectancy-consistent versus expectancy-inconsistent visual stimuli influence processing dynamics. Participants viewed images of faces, houses, and tools (Experiment 1), celebrity faces (Experiment 2), or animal faces (Experiment 3), preceded by a priming question. Notably, both conditions presented identical visual stimulation, ensuring that observed differences stemmed from cognitive processing rather than sensory input. Our results from Experiments 2 and 3 reveal that while the initial 150 ms period, crucial for unconscious face detection, remained unaffected, subsequent processing exhibited a delay of several milliseconds for expectancy-inconsistent stimuli, indicating additional processing time required for unexpected recognition. Importantly, no significant differences were observed in Experiment 1, where less demanding tasks or generic mental imagery were used, suggesting that the priming effect was not as pronounced in this context. These findings underscore the critical role of the period immediately following the first 150 ms in face identification and individuation, highlighting the influence of top-down attention on face recognition dynamics. This study provides novel insights into the temporal dynamics of face processing and the neural mechanisms underlying top-down attentional modulation.
{"title":"Modulation of face processing by top-down attention: Insights from early ERP waveforms","authors":"Nicolas M. Brunet, Britney M. Aguirre","doi":"10.1016/j.brainres.2024.149258","DOIUrl":"10.1016/j.brainres.2024.149258","url":null,"abstract":"<div><div>The face fusiform area (FFA) plays a pivotal role in face recognition, yet the precise timeline of its activity remains debated. Using EEG, we conducted three experiments to investigate how expectancy-consistent versus expectancy-inconsistent visual stimuli influence processing dynamics. Participants viewed images of faces, houses, and tools (Experiment 1), celebrity faces (Experiment 2), or animal faces (Experiment 3), preceded by a priming question. Notably, both conditions presented identical visual stimulation, ensuring that observed differences stemmed from cognitive processing rather than sensory input. Our results from Experiments 2 and 3 reveal that while the initial 150 ms period, crucial for unconscious face detection, remained unaffected, subsequent processing exhibited a delay of several milliseconds for expectancy-inconsistent stimuli, indicating additional processing time required for unexpected recognition. Importantly, no significant differences were observed in Experiment 1, where less demanding tasks or generic mental imagery were used, suggesting that the priming effect was not as pronounced in this context. These findings underscore the critical role of the period immediately following the first 150 ms in face identification and individuation, highlighting the influence of top-down attention on face recognition dynamics. This study provides novel insights into the temporal dynamics of face processing and the neural mechanisms underlying top-down attentional modulation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149258"},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375104","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}
Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.
{"title":"Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats","authors":"Taichi Goto , Tomokazu Tsurugizawa , Yuji Komaki , Ichiro Takashima , Sunao Iwaki , Nobuo Kunori","doi":"10.1016/j.brainres.2024.149257","DOIUrl":"10.1016/j.brainres.2024.149257","url":null,"abstract":"<div><div>Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149257"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370956","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 : 2024-09-26DOI: 10.1016/j.brainres.2024.149254
Jingji Wang , Xueqing Wang , Jun Yang , Yilan Zhen , Wenming Ban , Guoqi Zhu
Decrease of cerebral blood flow is the primary cause of vascular dementia (VD), but its pathophysiological mechanisms are still not known. This study aims to profile the molecular changes of a rat model of VD induced by bilateral common carotid artery ligation. The Morris water maze and new object recognition tasks were used to test the cognitive function of rats. Hematoxylin and Eosin (HE) staining was used to detect pathological changes in the hippocampus. After confirming the model, proteomics was used to detect differentially expressed proteins in the hippocampus, and metabolomics was used to detect differential metabolites in rat serum. Thereafter, bioinformatics were used to integrate and analyze the potential molecular profile. The results showed that compared with the sham control group, the spatial and recognition memory of the rats were significantly reduced, and pathological changes were observed in the hippocampal CA1 region of the model group. Proteomic analysis suggested 206 differentially expressed proteins in the hippocampus of VD rats, with 117 proteins upregulated and 89 downregulated. Protein-protein interaction network analysis suggested that those differentially expressed proteins might play crucial roles in lipid metabolism, cell adhesion, intracellular transport, and signal transduction. Metabolomics analysis identified 103 differential metabolites, and comparison with the human metabolome database revealed 22 common metabolites, which predicted 265 potential targets. Afterwards, by intersecting the predicted results from metabolomics with the differentially expressed proteins from proteomics, we identified five potential targets, namely ACE, GABBR1, Rock1, Abcc1 and Mapk10. Furthermore, western blotting confirmed that compared with control group, hippocampal GABBR1 and Rock1 were enhanced in the model group. Together, this study showed the molecular profile of VD rats through a combination of proteomics, metabolomics, and experimental confirmation methods, offering crucial molecular targets for the diagnosis and treatment of VD.
{"title":"Molecular profiling of a rat model of vascular dementia: Evidences from proteomics, metabolomics and experimental validations","authors":"Jingji Wang , Xueqing Wang , Jun Yang , Yilan Zhen , Wenming Ban , Guoqi Zhu","doi":"10.1016/j.brainres.2024.149254","DOIUrl":"10.1016/j.brainres.2024.149254","url":null,"abstract":"<div><div>Decrease of cerebral blood flow is the primary cause of vascular dementia (VD), but its pathophysiological mechanisms are still not known. This study aims to profile the molecular changes of a rat model of VD induced by bilateral common carotid artery ligation. The Morris water maze and new object recognition tasks were used to test the cognitive function of rats. Hematoxylin and Eosin (HE) staining was used to detect pathological changes in the hippocampus. After confirming the model, proteomics was used to detect differentially expressed proteins in the hippocampus, and metabolomics was used to detect differential metabolites in rat serum. Thereafter, bioinformatics were used to integrate and analyze the potential molecular profile. The results showed that compared with the sham control group, the spatial and recognition memory of the rats were significantly reduced, and pathological changes were observed in the hippocampal CA1 region of the model group. Proteomic analysis suggested 206 differentially expressed proteins in the hippocampus of VD rats, with 117 proteins upregulated and 89 downregulated. Protein-protein interaction network analysis suggested that those differentially expressed proteins might play crucial roles in lipid metabolism, cell adhesion, intracellular transport, and signal transduction. Metabolomics analysis identified 103 differential metabolites, and comparison with the human metabolome database revealed 22 common metabolites, which predicted 265 potential targets. Afterwards, by intersecting the predicted results from metabolomics with the differentially expressed proteins from proteomics, we identified five potential targets, namely ACE, GABBR1, Rock1, Abcc1 and Mapk10. Furthermore, western blotting confirmed that compared with control group, hippocampal GABBR1 and Rock1 were enhanced in the model group. Together, this study showed the molecular profile of VD rats through a combination of proteomics, metabolomics, and experimental confirmation methods, offering crucial molecular targets for the diagnosis and treatment of VD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149254"},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341511","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 : 2024-09-25DOI: 10.1016/j.brainres.2024.149253
Xiaohan Xu , Shuaili Xu , Yuan Gao , Shan He , Jiachen He , Xi Chen , Jiaqi Guo , Xuxiang Zhang
Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood–brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin. RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats, which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR.
{"title":"Remote ischemic conditioning slows blood-retinal barrier damage in type 1 diabetic rats","authors":"Xiaohan Xu , Shuaili Xu , Yuan Gao , Shan He , Jiachen He , Xi Chen , Jiaqi Guo , Xuxiang Zhang","doi":"10.1016/j.brainres.2024.149253","DOIUrl":"10.1016/j.brainres.2024.149253","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood–brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin. RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats, which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149253"},"PeriodicalIF":2.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341510","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 : 2024-09-24DOI: 10.1016/j.brainres.2024.149252
Xiaopei Zhang , Li Li , Yitong Li , Changzheng Dong , Jian Shi , Xiaoqiang Guo , Aixia Sui
Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.
{"title":"The role of trimethylation on histone H3 lysine 27 (H3K27me3) in temozolomide resistance of glioma","authors":"Xiaopei Zhang , Li Li , Yitong Li , Changzheng Dong , Jian Shi , Xiaoqiang Guo , Aixia Sui","doi":"10.1016/j.brainres.2024.149252","DOIUrl":"10.1016/j.brainres.2024.149252","url":null,"abstract":"<div><div>Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149252"},"PeriodicalIF":2.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323802","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 : 2024-09-21DOI: 10.1016/j.brainres.2024.149250
Kyoungjoo Cho , Gyung Whan Kim
This study delineated the intricate relation between cholesterol metabolism, protein degradation mechanisms, and the pathogenesis of Huntington’s disease (HD). Through investigations using both animal models and cellular systems, we have observed significant alterations in cholesterol levels, particularly in the striatum, which is the primary lesion site in HD. Our findings indicate the dysregulation of cholesterol metabolism-related factors, such as LDLR and SREBP2, in HD, which may contribute to disease progression. Additionally, we uncovered disruptions in protein degradation pathways, including decreased neddylated proteins and dysregulated autophagy, which further exacerbated HD pathology. Moreover, our study highlighted the potential therapeutic implications of targeting these pathways. By restoring cholesterol levels and modulating protein degradation mechanisms, particularly through interventions, such as MLN4924, we observed potential improvements in cellular function, as indicated by the increased BDNF levels. These insights underscore the importance of simultaneously addressing cholesterol metabolism and protein degradation to alleviate HD pathology. Collectively, this study provides a basic understanding of the interplay between the decrease of SREBP2 and the dysfunctional protein degradation system derived from disrupted cholesterol metabolism in HD and HD cells.
这项研究揭示了胆固醇代谢、蛋白质降解机制与亨廷顿氏病（HD）发病机制之间错综复杂的关系。通过使用动物模型和细胞系统进行研究，我们观察到胆固醇水平发生了显著变化，尤其是在纹状体中，而纹状体是 HD 的主要病变部位。我们的研究结果表明，胆固醇代谢相关因子（如 LDLR 和 SREBP2）在 HD 中的失调可能会导致疾病进展。此外，我们还发现了蛋白质降解途径的紊乱，包括内切酶蛋白减少和自噬失调，这进一步加剧了HD的病理变化。此外，我们的研究还强调了针对这些途径的潜在治疗意义。通过恢复胆固醇水平和调节蛋白质降解机制，特别是通过 MLN4924 等干预措施，我们观察到细胞功能的潜在改善，BDNF 水平的提高就表明了这一点。这些见解强调了同时解决胆固醇代谢和蛋白质降解问题以缓解 HD 病理学的重要性。总之，这项研究为我们提供了一个基本认识，即在 HD 和 HD 细胞中，SREBP2 的减少与胆固醇代谢紊乱导致的蛋白质降解系统功能失调之间的相互作用。
{"title":"Decreased SREBP2 of the striatal cell relates to disrupted protein degradation in Huntington’s disease","authors":"Kyoungjoo Cho , Gyung Whan Kim","doi":"10.1016/j.brainres.2024.149250","DOIUrl":"10.1016/j.brainres.2024.149250","url":null,"abstract":"<div><div>This study delineated the intricate relation between cholesterol metabolism, protein degradation mechanisms, and the pathogenesis of Huntington’s disease (HD). Through investigations using both animal models and cellular systems, we have observed significant alterations in cholesterol levels, particularly in the striatum, which is the primary lesion site in HD. Our findings indicate the dysregulation of cholesterol metabolism-related factors, such as LDLR and SREBP2, in HD, which may contribute to disease progression. Additionally, we uncovered disruptions in protein degradation pathways, including decreased neddylated proteins and dysregulated autophagy, which further exacerbated HD pathology. Moreover, our study highlighted the potential therapeutic implications of targeting these pathways. By restoring cholesterol levels and modulating protein degradation mechanisms, particularly through interventions, such as MLN4924, we observed potential improvements in cellular function, as indicated by the increased BDNF levels. These insights underscore the importance of simultaneously addressing cholesterol metabolism and protein degradation to alleviate HD pathology. Collectively, this study provides a basic understanding of the interplay between the decrease of SREBP2 and the dysfunctional protein degradation system derived from disrupted cholesterol metabolism in HD and HD cells.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149250"},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307122","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}
Sports trainers have recently shown increasing interest in innovative methods, including transcranial electric stimulation, to enhance motor performance and boost the acquisition of new skills during training. However, studies on the effectiveness of these tools on fast visuomotor learning and brain activity are still limited. In this randomized single-blind, sham-controlled, between-subjects study, we investigated whether a single training session, either coupled or not with 2 mA online high-frequency transcranial random noise stimulation (hf-tRNS) over the bilateral primary motor cortex (M1), would affect dart-throwing performance (i.e., radial error, arm range of motion, and movement variability) in 37 healthy volunteers. In addition, potential neurophysiological correlates were monitored before and after the training through a 32-electrode portable electroencephalogram (EEG). Results revealed that a single training session improved radial error and arm range of motion during the dart-throwing task, but not movement variability. Furthermore, after the training, resting state-EEG data showed a decrease in theta power. Radial error, arm movement, and EEG were not further modulated by hf-tRNS. This indicates that a single training session, regardless of hf-tRNS administration, improves dart-throwing precision and movement accuracy. However, it does not improve movement variability, which might require multiple training sessions (expertise resulting in slow learning). Theta power decrease could describe a more efficient use of cognitive resources (i.e., attention and visuomotor skills) due to the fast dart-throwing learning. Further research could explore different sports by applying longer stimulation protocols and evaluating other EEG variables to enhance our understanding of the lasting impacts of multi-session hf-tRNS on the sensorimotor cortex within the framework of slow learning and training assistance.
{"title":"Darts fast-learning reduces theta power but is not affected by Hf-tRNS: A behavioral and electrophysiological investigation","authors":"Giorgia Francesca Scaramuzzi , Anna Concetta Spina , Valerio Manippa , Francesca Amico , Ester Cornacchia , Annalisa Palmisano , Gaetano Scianatico , Richard Buscombe , Richard Avery , Volker Thoma , Davide Rivolta","doi":"10.1016/j.brainres.2024.149249","DOIUrl":"10.1016/j.brainres.2024.149249","url":null,"abstract":"<div><div>Sports trainers have recently shown increasing interest in innovative methods, including transcranial electric stimulation, to enhance motor performance and boost the acquisition of new skills during training. However, studies on the effectiveness of these tools on fast visuomotor learning and brain activity are still limited. In this randomized single-blind, sham-controlled, between-subjects study, we investigated whether a single training session, either coupled or not with 2 mA online high-frequency transcranial random noise stimulation (hf-tRNS) over the bilateral primary motor cortex (M1), would affect dart-throwing performance (i.e., radial error, arm range of motion, and movement variability) in 37 healthy volunteers. In addition, potential neurophysiological correlates were monitored before and after the training through a 32-electrode portable electroencephalogram (EEG). Results revealed that a single training session improved radial error and arm range of motion during the dart-throwing task, but not movement variability. Furthermore, after the training, resting state-EEG data showed a decrease in theta power. Radial error, arm movement, and EEG were not further modulated by hf-tRNS. This indicates that a single training session, regardless of hf-tRNS administration, improves dart-throwing precision and movement accuracy. However, it does not improve movement variability, which might require multiple training sessions (expertise resulting in slow learning). Theta power decrease could describe a more efficient use of cognitive resources (i.e., attention and visuomotor skills) due to the fast dart-throwing learning. Further research could explore different sports by applying longer stimulation protocols and evaluating other EEG variables to enhance our understanding of the lasting impacts of multi-session hf-tRNS on the sensorimotor cortex within the framework of slow learning and training assistance.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149249"},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307121","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}
Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.
{"title":"Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish","authors":"Yang-Jin Shen , Hao-Yuan Chen , Chia-Wei Chang , Yin-Cheng Huang , Yi-Chuan Cheng","doi":"10.1016/j.brainres.2024.149248","DOIUrl":"10.1016/j.brainres.2024.149248","url":null,"abstract":"<div><div>Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149248"},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307120","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 : 2024-09-19DOI: 10.1016/j.brainres.2024.149245
Wireko Andrew Awuah , Adam Ben-Jaafar , Jonathan Sing Huk Kong , Vivek Sanker , Muhammad Hamza Shah , Jeisun Poornaselvan , Mabel Frimpong , Shahzeb Imran , Tony Alocious , Toufik Abdul-Rahman , Oday Atallah
Cerebrovascular diseases (CVDs) include conditions such as stroke, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD), which contribute significantly to global morbidity and healthcare burden. The pathophysiology of CVD is complex, involving inflammatory, cellular and vascular mechanisms. Recently, research has focused on triggering receptor expressed on myeloid cells 2 (TREM2), an immune receptor predominantly found on microglia. TREM2 interacts with multiple signalling pathways, particularly toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), inhibiting patients’ inflammatory response. This receptor plays an essential role in both immune regulation and neuroprotection. TREM2 deficiency or dysfunction is associated with impaired microglial responses, exacerbated neurodegeneration and neuroinflammation. Up until recently, TREM2 related studies have focused on neurodegenerative diseases (NDs), however a shift in focus towards CVDs is beginning to take place. Advancements in CVD research have focused on developing therapeutic strategies targeting TREM2 to enhance recovery and reduce long-term deficits. These include the exploration of TREM2 agonists and combination therapies with other anti-inflammatory agents, which may synergistically reduce neuroinflammation and promote neuroprotection. The modulation of TREM2 activity holds potential for innovative treatment approaches aimed at improving patient outcomes following cerebrovascular insults. This review compiles current research on TREM2, emphasising its molecular mechanisms, therapeutic potential, and advancements in CNS disease research.
{"title":"Novel insights into the role of TREM2 in cerebrovascular diseases","authors":"Wireko Andrew Awuah , Adam Ben-Jaafar , Jonathan Sing Huk Kong , Vivek Sanker , Muhammad Hamza Shah , Jeisun Poornaselvan , Mabel Frimpong , Shahzeb Imran , Tony Alocious , Toufik Abdul-Rahman , Oday Atallah","doi":"10.1016/j.brainres.2024.149245","DOIUrl":"10.1016/j.brainres.2024.149245","url":null,"abstract":"<div><p>Cerebrovascular diseases (CVDs) include conditions such as stroke, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD), which contribute significantly to global morbidity and healthcare burden. The pathophysiology of CVD is complex, involving inflammatory, cellular and vascular mechanisms. Recently, research has focused on triggering receptor expressed on myeloid cells 2 (TREM2), an immune receptor predominantly found on microglia. TREM2 interacts with multiple signalling pathways, particularly toll-like receptor 4 (<em>TLR4</em>) and nuclear factor kappa B (<em>NF-κB)</em>, inhibiting patients’ inflammatory response. This receptor plays an essential role in both immune regulation and neuroprotection. TREM2 deficiency or dysfunction is associated with impaired microglial responses, exacerbated neurodegeneration and neuroinflammation. Up until recently, TREM2 related studies have focused on neurodegenerative diseases (NDs), however a shift in focus towards CVDs is beginning to take place. Advancements in CVD research have focused on developing therapeutic strategies targeting TREM2 to enhance recovery and reduce long-term deficits. These include the exploration of TREM2 agonists and combination therapies with other anti-inflammatory agents, which may synergistically reduce neuroinflammation and promote neuroprotection. The modulation of TREM2 activity holds potential for innovative treatment approaches aimed at improving patient outcomes following cerebrovascular insults. This review compiles current research on TREM2, emphasising its molecular mechanisms, therapeutic potential, and advancements in CNS disease research.</p></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149245"},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0006899324004992/pdfft?md5=78f5307953b5517be692b64c89e128ad&pid=1-s2.0-S0006899324004992-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272691","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 : 2024-09-18DOI: 10.1016/j.brainres.2024.149247
Bruna Teixeira-Silva , Giovanna Varzea Roberti Monteiro de Mattos , Vinicius de Frias Carvalho , Paula Campello-Costa
During early life, disruptions in glutamatergic and GABAergic synapse development in the hippocampus may contribute to several neurodevelopmental disorders, including cognitive deficits and psychiatric disorders. Caffeine is the most consumed psychoactive drug in the world, and previous work from our group has shown that caffeine disrupts visual system connections at different stages of development. This work aimed to investigate the effects of caffeine consumption during lactation in the glutamatergic and GABAergic synaptic markers in the hippocampus and on the behavior of rat offspring. We found that maternal caffeine intake significantly reduced GluN1 subunits of the NMDA receptor, increased the GluA1/GluA2 ratio of AMPA receptor in the dorsal hippocampus, and decreased GAD content in female pups’ ventral hippocampus. On the other hand, an increase in GluN1/GluN2b subunits, a decrease in GAD content in the dorsal hippocampus, and a reduction of the GluA1 content in the ventral hippocampus were observed in male pups. In addition, changes in the behavior of the offspring submitted to indirect caffeine consumption were also sex-dependent, with females developing anxiety-like behavior and males showing anxiety-like behavior and hyper-locomotion. These results highlight that maternal caffeine intake promotes changes in the hippocampal excitatory and inhibitory balance and offspring behavior in a sex-dependent manner, suggesting that the population should be alerted to reduced caffeine consumption by breastfeeding mothers.
{"title":"Caffeine intake during lactation has a sex-dependent effect on the hippocampal excitatory/inhibitory balance and pups’ behavior","authors":"Bruna Teixeira-Silva , Giovanna Varzea Roberti Monteiro de Mattos , Vinicius de Frias Carvalho , Paula Campello-Costa","doi":"10.1016/j.brainres.2024.149247","DOIUrl":"10.1016/j.brainres.2024.149247","url":null,"abstract":"<div><div>During early life, disruptions in glutamatergic and GABAergic synapse development in the hippocampus may contribute to several neurodevelopmental disorders, including cognitive deficits and psychiatric disorders. Caffeine is the most consumed psychoactive drug in the world, and previous work from our group has shown that caffeine disrupts visual system connections at different stages of development. This work aimed to investigate the effects of caffeine consumption during lactation in the glutamatergic and GABAergic synaptic markers in the hippocampus and on the behavior of rat offspring. We found that maternal caffeine intake significantly reduced GluN1 subunits of the NMDA receptor, increased the GluA1/GluA2 ratio of AMPA receptor in the dorsal hippocampus, and decreased GAD content in female pups’ ventral hippocampus. On the other hand, an increase in GluN1/GluN2b subunits, a decrease in GAD content in the dorsal hippocampus, and a reduction of the GluA1 content in the ventral hippocampus were observed in male pups. In addition, changes in the behavior of the offspring submitted to indirect caffeine consumption were also sex-dependent, with females developing anxiety-like behavior and males showing anxiety-like behavior and hyper-locomotion. These results highlight that maternal caffeine intake promotes changes in the hippocampal excitatory and inhibitory balance and offspring behavior in a sex-dependent manner, suggesting that the population should be alerted to reduced caffeine consumption by breastfeeding mothers.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149247"},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280221","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}
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