Pub Date : 2025-11-04DOI: 10.1016/j.brainres.2025.150027
Puyuan Zhang , Shelley Xiuli Tong
The human brain automatically detects likely connections between environmental inputs through statistical learning, which involves multiple neural mechanisms. However, how these neural mechanisms adapt to the specific patterns of exemplars remains unclear. Using electroencephalography (EEG) combined with a probabilistic cueing task, this study investigated how the transitional probability (TP) of inputs (i.e., the likelihood that one input will be followed by another in a sequence) influenced neural responses to probabilistic associations. Time-frequency analysis revealed that when highly probable associations occurred after high-TP inputs, reduced alpha-/beta-band desynchronized activity was observed in parietal regions. Conversely, when high-probable associations occurred after low-TP inputs, theta-band activity increased in frontal regions. Additionally, after low-TP inputs, low-probability associations decreased theta-band activity in parietal regions but elicited a larger N1 effect in frontal regions. These results clarify how neural mechanisms adapt to learned associations and minimize prediction errors, supporting a dual-process framework of statistical learning driven by input characteristics.
{"title":"Distinct neural mechanisms of probabilistic processing in visual statistical learning","authors":"Puyuan Zhang , Shelley Xiuli Tong","doi":"10.1016/j.brainres.2025.150027","DOIUrl":"10.1016/j.brainres.2025.150027","url":null,"abstract":"<div><div>The human brain automatically detects likely connections between environmental inputs through statistical learning, which involves multiple neural mechanisms. However, how these neural mechanisms adapt to the specific patterns of exemplars remains unclear. Using electroencephalography (EEG) combined with a probabilistic cueing task, this study investigated how the transitional probability (TP) of inputs (i.e., the likelihood that one input will be followed by another in a sequence) influenced neural responses to probabilistic associations. Time-frequency analysis revealed that when highly probable associations occurred after high-TP inputs, reduced alpha-/beta-band desynchronized activity was observed in parietal regions. Conversely, when high-probable associations occurred after low-TP inputs, theta-band activity increased in frontal regions. Additionally, after low-TP inputs, low-probability associations decreased theta-band activity in parietal regions but elicited a larger N1 effect in frontal regions. These results clarify how neural mechanisms adapt to learned associations and minimize prediction errors, supporting a dual-process framework of statistical learning driven by input characteristics.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150027"},"PeriodicalIF":2.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450660","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 : 2025-11-04DOI: 10.1016/j.brainres.2025.150034
Hyunha Choi , Subin Hwang , Hyeyeon Cho , Sunjoo Ahn , Hwi-yeol Yun , Jin Sook Song
Memantine, an NMDA receptor antagonist clinically approved for Alzheimer’s disease, has been implicated in modulating neuroinflammatory responses beyond its anti-excitotoxic actions. To explore its potential relevance in Parkinson’s disease, this study evaluated memantine’s effects in both LPS-activated microglial cells and a synucleinopathy mouse model. In BV-2 cells, memantine elicited a modest but measurable attenuation of TNF-α and IL-6 secretion, which was accompanied by downregulation of TLR4 and IκB signaling. In vivo, 5-month oral administration of memantine to mThy1-αSyn transgenic mice led to moderate improvements in motor function as assessed by beam-walk performance. Immunohistochemical analyses revealed decreased microglial activation in the cerebral cortex; however, phosphorylated α-synuclein accumulation and tyrosine hydroxylase expression remained unaffected. Furthermore, spatial working memory was not improved by treatment. Taken together, these findings suggest that memantine may exert beneficial effects on neuroinflammatory processes and behavioral deficits in PD-relevant models. However, its impact on the hallmark neuropathology of PD appears limited.
{"title":"Memantine modulates neuroinflammation and motor coordination in a Parkinson’s disease model","authors":"Hyunha Choi , Subin Hwang , Hyeyeon Cho , Sunjoo Ahn , Hwi-yeol Yun , Jin Sook Song","doi":"10.1016/j.brainres.2025.150034","DOIUrl":"10.1016/j.brainres.2025.150034","url":null,"abstract":"<div><div>Memantine, an NMDA receptor antagonist clinically approved for Alzheimer’s disease, has been implicated in modulating neuroinflammatory responses beyond its anti-excitotoxic actions. To explore its potential relevance in Parkinson’s disease, this study evaluated memantine’s effects in both LPS-activated microglial cells and a synucleinopathy mouse model. In BV-2 cells, memantine elicited a modest but measurable attenuation of TNF-α and IL-6 secretion, which was accompanied by downregulation of TLR4 and IκB signaling. In vivo, 5-month oral administration of memantine to mThy1-αSyn transgenic mice led to moderate improvements in motor function as assessed by beam-walk performance. Immunohistochemical analyses revealed decreased microglial activation in the cerebral cortex; however, phosphorylated α-synuclein accumulation and tyrosine hydroxylase expression remained unaffected. Furthermore, spatial working memory was not improved by treatment. Taken together, these findings suggest that memantine may exert beneficial effects on neuroinflammatory processes and behavioral deficits in PD-relevant models. However, its impact on the hallmark neuropathology of PD appears limited.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150034"},"PeriodicalIF":2.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457474","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}
Major Depressive Disorder (MDD) is a prevalent chronic mental illness worldwide. Antidepressants are a fundamental part of their treatment, being effective in 60–70 % of patients. Alternative therapies, such as repetitive transcranial magnetic stimulation (rTMS), have also been proposed for modulating cortical neuronal activity and activating circuits associated with the stimulated area. Dopamine is one of the principal neurotransmitters in the nigrostriatal pathway. Changes in dopaminergic transmission through the mesolimbic pathway have been identified as part of the pathophysiology of depression; however, there are only a small number of studies examining the relationship between the nigrostriatal pathway and depression. This study aims to describe the effect of rTMS on the dorsal striatum and prefrontal cortex in a rat model of depression. Behaviors associated with the developed depression and anxiety were assessed through a test battery consisting of sucrose preference, forced swimming, open field, and elevated plus maze. The 10 Hz rTMS was applied daily for 15 days, and behavioral tests were re-evaluated. The brains were obtained and analyzed through immunofluorescence labeling of tyrosine hydroxylase and dopamine D2 receptors. It was observed that rTMS reduces depression-like behaviors. Dopamine D2 receptor density decreased in the dorsal striatum and prefrontal cortex of rats that received treatment compared to those with sham stimulation and untreated animals. These results indicate that rTMS affects not only the stimulated region but also influences the dorsal striatum. This finding might contribute to improving the anti-depressive behavior observed in the chronic unpredictable mild stress rat model.
{"title":"High-frequency transcranial magnetic stimulation decreases dorsal striatum dopamine D2 receptors in a rat model of depression","authors":"Palma-Anzures Irving Eduardo , Verdugo-Diaz Leticia","doi":"10.1016/j.brainres.2025.150016","DOIUrl":"10.1016/j.brainres.2025.150016","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a prevalent chronic mental illness worldwide. Antidepressants are a fundamental part of their treatment, being effective in 60–70 % of patients. Alternative therapies, such as repetitive transcranial magnetic stimulation (rTMS), have also been proposed for modulating cortical neuronal activity and activating circuits associated with the stimulated area. Dopamine is one of the principal neurotransmitters in the nigrostriatal pathway. Changes in dopaminergic transmission through the mesolimbic pathway have been identified as part of the pathophysiology of depression; however, there are only a small number of studies examining the relationship between the nigrostriatal pathway and depression. This study aims to describe the effect of rTMS on the dorsal striatum and prefrontal cortex in a rat model of depression. Behaviors associated with the developed depression and anxiety were assessed through a test battery consisting of sucrose preference, forced swimming, open field, and elevated plus maze.<!--> <!-->The<!--> <!-->10 Hz rTMS was applied daily for 15 days, and behavioral tests were re-evaluated. The brains were obtained and analyzed through immunofluorescence labeling of tyrosine hydroxylase and dopamine D2 receptors. It was observed that rTMS reduces depression-like behaviors.<!--> <!-->Dopamine D2 receptor density decreased in the dorsal striatum and prefrontal cortex of rats that received treatment compared to those with sham stimulation and untreated animals. These results indicate that rTMS affects not only the stimulated region but also influences the dorsal striatum. This finding might contribute to improving the anti-depressive behavior observed in the chronic unpredictable mild stress rat model.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150016"},"PeriodicalIF":2.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457424","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}
Frequent object dropping is a common complaint in patients with carpal tunnel syndrome (CTS), suggesting potential disruptions in sensorimotor integration. This study investigated the electrophysiological characteristics of sensorimotor integration in CTS patients with and without this symptom. We enrolled twelve CTS patients with frequent object dropping (dCTS), ten CTS patients without noticeable clumsiness (ndCTS), and sixteen healthy controls. All participants underwent clinical evaluation, the Boston Carpal Tunnel Questionnaire, and the Purdue Pegboard Test. To assess sensorimotor integration, electrical stimulation was applied to the median and ulnar nerves, followed by transcranial magnetic stimulation over the contralateral motor cortex at interstimulus intervals (ISIs) of 20, 35, 50, 65, 80, 100, and 200 ms. Motor-evoked potentials (MEPs) were recorded from the thenar and hypothenar muscles. Key findings revealed distinct sensorimotor integration patterns on the dominant side. In the dCTS group, median nerve stimulation at a 35 ms ISI resulted in significantly higher MEP amplitude ratios in the thenar muscles compared to controls. Conversely, in the ndCTS group, ulnar nerve stimulation at ISIs of 20, 80, and 100 ms produced greater MEP ratios in the same muscles. These results demonstrate topographically divergent cortical sensory processing between dCTS and ndCTS patients. One interpretation of these findings is that altered sensorimotor integration from the median nerve underlies the clumsiness in dCTS, while patients without this symptom (ndCTS) may successfully compensate by utilizing sensory input from the ulnar nerve.
频繁的物体掉落是腕管综合征（CTS）患者的常见主诉，提示感觉运动整合的潜在中断。本研究探讨了有和无此症状的CTS患者感觉运动整合的电生理特征。我们招募了12名经常掉落物体的CTS患者（dCTS）， 10名无明显笨拙的CTS患者（ndCTS）和16名健康对照。所有的参与者都进行了临床评估、波士顿腕管调查问卷和普渡钉板测试。为了评估感觉运动整合，对正中神经和尺神经进行电刺激，然后在20、35、50、65、80、100和200 ms的刺激间隔（ISIs）对侧运动皮层进行经颅磁刺激。记录大鱼际和下鱼际肌肉运动诱发电位（MEPs）。主要发现揭示了显性侧明显的感觉运动整合模式。在dCTS组中，与对照组相比，35 ms ISI的正中神经刺激导致大足底肌肉的MEP振幅比显着提高。相反，在ndCTS组中，ISIs为20,80和100 ms时的尺神经刺激在相同肌肉中产生了更高的MEP比率。这些结果表明在dCTS和ndCTS患者之间皮层感觉加工在地形上存在差异。对这些发现的一种解释是，正中神经感觉运动整合的改变是dCTS笨拙的基础，而没有这种症状的患者（ndCTS）可以通过利用尺神经的感觉输入成功地进行补偿。
{"title":"Frequent object dropping in carpal tunnel syndrome: a consequence of impaired sensorimotor integration?","authors":"Zeliha Matur , Nimet Dörtcan , Sertaç İmişçi , Melis Süner , Zeynep Acar , Nejla Sözer , Ali Emre Öge","doi":"10.1016/j.brainres.2025.150029","DOIUrl":"10.1016/j.brainres.2025.150029","url":null,"abstract":"<div><div>Frequent object dropping is a common complaint in patients with carpal tunnel syndrome (CTS), suggesting potential disruptions in sensorimotor integration. This study investigated the electrophysiological characteristics of sensorimotor integration in CTS patients with and without this symptom. We enrolled twelve CTS patients with frequent object dropping (dCTS), ten CTS patients without noticeable clumsiness (ndCTS), and sixteen healthy controls. All participants underwent clinical evaluation, the Boston Carpal Tunnel Questionnaire, and the Purdue Pegboard Test. To assess sensorimotor integration, electrical stimulation was applied to the median and ulnar nerves, followed by transcranial magnetic stimulation over the contralateral motor cortex at interstimulus intervals (ISIs) of 20, 35, 50, 65, 80, 100, and 200 ms. Motor-evoked potentials (MEPs) were recorded from the thenar and hypothenar muscles. Key findings revealed distinct sensorimotor integration patterns on the dominant side. In the dCTS group, median nerve stimulation at a 35 ms ISI resulted in significantly higher MEP amplitude ratios in the thenar muscles compared to controls. Conversely, in the ndCTS group, ulnar nerve stimulation at ISIs of 20, 80, and 100 ms produced greater MEP ratios in the same muscles. These results demonstrate topographically divergent cortical sensory processing between dCTS and ndCTS patients. One interpretation of these findings is that altered sensorimotor integration from the median nerve underlies the clumsiness in dCTS, while patients without this symptom (ndCTS) may successfully compensate by utilizing sensory input from the ulnar nerve.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150029"},"PeriodicalIF":2.6,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443891","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 : 2025-11-01DOI: 10.1016/j.brainres.2025.150030
M. Ashwin Kumar, G. Manikandan, L. Richard, P. Sanjana
The abnormal growth of cells inside or near the brain is called a brain tumor. Brain tumors can be benign (non-cancerous) or malignant (cancerous). Both these types can exert pressure on the surrounding brain tissue, increasing intracranial pressure. As the tumor grows, it presses on the nerves and brain tissues, causing symptoms like persistent headaches, seizures, vision or hearing issues and changes in personality, coordination and balance, these of which will completely ruin the normal life of people. Since treating these tumors is very difficult at the late stages, it is highly significant to find them at the early stages. Understanding the importance of early identification of brain tumors, a fuzzy logic-based ensemble method using Convolutional Neural Networks (CNN) named Fuzzy Guided Ensemble Inference System (FGEIS) is proposed. It is developed to identify tumors from MRI images with a high success rate. The FGEIS approach uses ensemble learning that encompasses variants of four different architectures – Densenet, Resnet, VGG, and Mobilenet. While Resnet’s residual connections allow for effective hierarchical feature learning for a variety of tumor types, Densenet supports feature reuse by collecting fine-grained tumor textures. The model is suitable for clinical usage because VGG prioritizes local spatial details that are important for accurate tumor localization, while mobilenet provides computing efficiency. These high-performing models are then integrated and applied through a fuzzy logic system. The experiments show improved performance of ensemble models over individual models with higher classification accuracy of 99.85 percentage.
{"title":"Fuzzy guided ensemble inference system for brain tumor classification","authors":"M. Ashwin Kumar, G. Manikandan, L. Richard, P. Sanjana","doi":"10.1016/j.brainres.2025.150030","DOIUrl":"10.1016/j.brainres.2025.150030","url":null,"abstract":"<div><div>The abnormal growth of cells inside or near the brain is called a brain tumor. Brain tumors can be benign (non-cancerous) or malignant (cancerous). Both these types can exert pressure on the surrounding brain tissue, increasing intracranial pressure. As the tumor grows, it presses on the nerves and brain tissues, causing symptoms like persistent headaches, seizures, vision or hearing issues and changes in personality, coordination and balance, these of which will completely ruin the normal life of people. Since treating these tumors is very difficult at the late stages, it is highly significant to find them at the early stages. Understanding the importance of early identification of brain tumors, a fuzzy logic-based ensemble method using Convolutional Neural Networks (CNN) named Fuzzy Guided Ensemble Inference System (FGEIS) is proposed. It is developed to identify tumors from MRI images with a high success rate. The FGEIS approach uses ensemble learning that encompasses variants of four different architectures – Densenet, Resnet, VGG, and Mobilenet. While Resnet’s residual connections allow for effective hierarchical feature learning for a variety of tumor types, Densenet supports feature reuse by collecting fine-grained tumor textures. The model is suitable for clinical usage because VGG prioritizes local spatial details that are important for accurate tumor localization, while mobilenet provides computing efficiency. These high-performing models are then integrated and applied through a fuzzy logic system. The experiments show improved performance of ensemble models over individual models with higher classification accuracy of 99.85 percentage.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150030"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430381","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 : 2025-11-01DOI: 10.1016/j.brainres.2025.150028
Genevieve Z. Steiner-Lim , Jack S. Fogarty , Robert J. Barry , Frances M. De Blasio
The aim of this study was to explore the mechanism of the age-related P3 anterior shift using high-precision temporal principal components analysis (tPCA). Continuous EEG was recorded from younger and older adults while completing a two-stimulus visual oddball task. tPCA input was narrowed to the P3 range to enhance precision and reveal potentially overlapping temporal components. eLORETA modelled group and condition-related differences in component sources to further understanding of the neurobiology of the P3 anterior shift. Target P3a, P3b and nontarget P3/l-P3 (late P3) evidenced the expected anterior shift. P3 component amplitudes were reduced for older compared to younger adults across both stimulus types, consistent with the P3 ‘ageing effect’. All P3 components showed age-related differences in activation in multiple and diffuse sources, indicating neural processing beyond frontal regions (i.e., neural broadening). Findings suggest a dedifferentiation rather than compensation mechanism, as reduced P3 target amplitudes reflect attenuated responding to a preferred stimulus, and the anterior shift to nontargets indicates decreased processing selectivity to a non-preferred stimulus.
{"title":"Exploring the mechanism of the age-related P3 anterior shift","authors":"Genevieve Z. Steiner-Lim , Jack S. Fogarty , Robert J. Barry , Frances M. De Blasio","doi":"10.1016/j.brainres.2025.150028","DOIUrl":"10.1016/j.brainres.2025.150028","url":null,"abstract":"<div><div>The aim of this study was to explore the mechanism of the age-related P3 anterior shift using high-precision temporal principal components analysis (tPCA). Continuous EEG was recorded from younger and older adults while completing a two-stimulus visual oddball task. tPCA input was narrowed to the P3 range to enhance precision and reveal potentially overlapping temporal components. eLORETA modelled group and condition-related differences in component sources to further understanding of the neurobiology of the P3 anterior shift. Target P3a, P3b and nontarget P3/l-P3 (late P3) evidenced the expected anterior shift. P3 component amplitudes were reduced for older compared to younger adults across both stimulus types, consistent with the P3 ‘ageing effect’. All P3 components showed age-related differences in activation in multiple and diffuse sources, indicating neural processing beyond frontal regions (i.e., neural broadening). Findings suggest a dedifferentiation rather than compensation mechanism, as reduced P3 target amplitudes reflect attenuated responding to a preferred stimulus, and the anterior shift to nontargets indicates decreased processing selectivity to a non-preferred stimulus.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150028"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430327","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 : 2025-10-31DOI: 10.1016/j.brainres.2025.150008
Li Huang , Jianzhong Shu , Qian Chen, Jinrong Li
Objective
Parkinson’s disease (PD) is a highly prevalent degenerative disease of the nervous system, with symptoms of motor retardation and balance disorders. This study aimed to investigate the Erbai decoction on PD rats and explore the underlying mechanism. Methods: SD rats were divided into five groups, including control, PD, PD + L-Erbai decoction, PD + H-Erbai decoction, and PD + Madopar. Drug treatment was employed with PD rats for 30 days. Firstly, behavioral experiments including the open field test (OFT), pole climbing, tail suspension test (TST), and Morris Water Maze (MWM) were performed. Next, the substantia nigra pars compacta (SNpc) of rats was obtained for H&E and Immunofluorescence (IF) staining, Tunnel, Transmission electron microscopy (TEM), Enzyme-linked immunosorbent assay (ELISA), Flow cytometry, Real-time fluorescence quantitative PCR (RT-qPCR), and Western blotting (WB) assays. Finally, the components of Erbai serum were determined by HPLC-QTOF/MS/MS assay. Results: For the behavioral experiments, it was found that Erbai decoction could enhance the balance and recognition abilities of PD rats. The results of HE and Tunnel revealed that Erbai decoction reversed the rotenone-induced pathological injury of SNpc. In addition, compared with the PD group, the PD + H-Erbai decoction group showed a higher level of autophagy and an inhibition of mitochondrial damage. Moreover, Erbai decoction treatment reversed PD modeling-induced p38 MAPK up-regulation and Parkin down-regulation, and the decrease of Parkin recruitment in mitochondria. Importantly, Erbai decoction and Madopar have similar pharmacological effects. 320 unique components of Erbai serum were identified. Conclusion: Erbai decoction could alleviate the SNpc injury by activating mitophagy in PD rats, and it may relate to the regulation of the p38 MAPK/Parkin signaling pathway.
目的：帕金森病（PD）是一种高度流行的神经系统退行性疾病，以运动迟缓和平衡障碍为症状。本研究旨在观察二白汤对帕金森病大鼠的影响，并探讨其作用机制。方法：SD大鼠分为对照组、PD组、PD + l -二白汤组、PD + h -二白汤组、PD + 美多巴组。PD大鼠用药30 d。首先进行行为学实验，包括空地测试（OFT）、爬杆、悬尾测试（TST）和Morris水迷宫（MWM）。接下来，取大鼠致密黑质（SNpc）进行H&E和免疫荧光（IF）染色、隧道显微镜、透射电镜（TEM）、酶联免疫吸附试验（ELISA）、流式细胞术、实时荧光定量PCR （RT-qPCR）和Western blotting （WB）检测。最后采用HPLC-QTOF/MS/MS法测定二白血清的成分。结果：行为学实验发现，二白汤能增强PD大鼠的平衡能力和认知能力。HE和Tunnel结果显示，二白汤对鱼藤酮诱导的SNpc病理损伤有逆转作用。此外，与PD组相比，PD + h -二白汤组表现出更高水平的自噬和线粒体损伤的抑制。此外，二白汤治疗可逆转PD模型诱导的p38 MAPK上调和Parkin下调，以及线粒体中Parkin募集的减少。重要的是，二白汤与美多巴具有相似的药理作用。鉴定出320种二白血清的独特成分。结论：二白汤可通过激活线粒体自噬来减轻PD大鼠SNpc损伤，其机制可能与调节p38 MAPK/Parkin信号通路有关。
{"title":"The underlying mechanism of Erbai decoction on Parkinson’s disease rats: a behavioral and pathological study","authors":"Li Huang , Jianzhong Shu , Qian Chen, Jinrong Li","doi":"10.1016/j.brainres.2025.150008","DOIUrl":"10.1016/j.brainres.2025.150008","url":null,"abstract":"<div><h3>Objective</h3><div>Parkinson’s disease (PD) is a highly prevalent degenerative disease of the nervous system, with symptoms of motor retardation and balance disorders. This study aimed to investigate the Erbai decoction on PD rats and explore the underlying mechanism. <strong>Methods:</strong> SD rats were divided into five groups, including control, PD, PD + L-Erbai decoction, PD + H-Erbai decoction, and PD + Madopar. Drug treatment was employed with PD rats for 30 days. Firstly, behavioral experiments including the open field test (OFT), pole climbing, tail suspension test (TST), and Morris Water Maze (MWM) were performed. Next, the substantia nigra pars compacta (SNpc) of rats was obtained for H&E and Immunofluorescence (IF) staining, Tunnel, Transmission electron microscopy (TEM), Enzyme-linked immunosorbent assay (ELISA), Flow cytometry, Real-time fluorescence quantitative PCR (RT-qPCR), and Western blotting (WB) assays. Finally, the components of Erbai serum were determined by HPLC-QTOF/MS/MS assay. <strong>Results:</strong> For the behavioral experiments, it was found that Erbai decoction could enhance the balance and recognition abilities of PD rats. The results of HE and Tunnel revealed that Erbai decoction reversed the rotenone-induced pathological injury of SNpc. In addition, compared with the PD group, the PD + H-Erbai decoction group showed a higher level of autophagy and an inhibition of mitochondrial damage. Moreover, Erbai decoction treatment reversed PD modeling-induced p38 MAPK up-regulation and Parkin down-regulation, and the decrease of Parkin recruitment in mitochondria. Importantly, Erbai decoction and Madopar have similar pharmacological effects. 320 unique components of Erbai serum were identified. <strong>Conclusion:</strong> Erbai decoction could alleviate the SNpc injury by activating mitophagy in PD rats, and it may relate to the regulation of the p38 MAPK/Parkin signaling pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1870 ","pages":"Article 150008"},"PeriodicalIF":2.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430394","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 : 2025-10-30DOI: 10.1016/j.brainres.2025.150012
Yeasmin Akter Munni, Khoa Nguyen Tran, In-Jun Yang
Major depression is associated with hippocampal pathology induced by prolonged exposure to stress hormones; yet, research predominantly utilizes animal models, which entail considerable costs, time, and translational constraints. While various studies have been conducted to investigate the neurotoxic effects of CORT, these research efforts have frequently been dispersed, concentrating on single endpoints or making use of immortalized cell lines that are less relevant. As a result, these studies have not adequately represented the integrated nature of neuronal dysfunction. To address this, we established and verified a complete, multi-parametric in vitro model involving the use of primary hippocampal neurons that were treated with corticosterone. This study effectively incorporates various aspects of stress-induced neuropathology. Our integrated approach demonstrates that corticosterone treatment resulted in concentration-dependent reductions in neuronal viability, increased reactive oxygen species production, disrupted mitochondrial membrane potential, attenuated neurite outgrowth, and impaired neuronal polarization. Furthermore, corticosterone significantly downregulated expression of key neurogenic markers (BDNF, TrkB, and DCX), mirroring the neurotrophic deficits observed in depression. The model demonstrated predictive validity through its response to fluoxetine, which ameliorated neuronal differentiation impairments and restored neurotrophic signaling. This primary hippocampal neuron-corticosterone system offers researchers an efficient platform for mechanistic investigations and preliminary screening of potential antidepressant compounds, potentially facilitating more targeted subsequent in vivo studies while reducing animal usage. By replicating multiple aspects of stress-induced neuronal dysfunction, it represents a valuable tool for depression research and therapeutic development.
{"title":"Corticosterone-induced neuronal dysfunction in hippocampal cultures: a novel in vitro model for stress-related neuronal pathology research","authors":"Yeasmin Akter Munni, Khoa Nguyen Tran, In-Jun Yang","doi":"10.1016/j.brainres.2025.150012","DOIUrl":"10.1016/j.brainres.2025.150012","url":null,"abstract":"<div><div>Major depression is associated with hippocampal pathology induced by prolonged exposure to stress hormones; yet, research predominantly utilizes animal models, which entail considerable costs, time, and translational constraints. While various studies have been conducted to investigate the neurotoxic effects of CORT, these research efforts have frequently been dispersed, concentrating on single endpoints or making use of immortalized cell lines that are less relevant. As a result, these studies have not adequately represented the integrated nature of neuronal dysfunction. To address this, we established and verified a complete, multi-parametric in vitro model involving the use of primary hippocampal neurons that were treated with corticosterone. This study effectively incorporates various aspects of stress-induced neuropathology. Our integrated approach demonstrates that corticosterone treatment resulted in concentration-dependent reductions in neuronal viability, increased reactive oxygen species production, disrupted mitochondrial membrane potential, attenuated neurite outgrowth, and impaired neuronal polarization. Furthermore, corticosterone significantly downregulated expression of key neurogenic markers (BDNF, TrkB, and DCX), mirroring the neurotrophic deficits observed in depression. The model demonstrated predictive validity through its response to fluoxetine, which ameliorated neuronal differentiation impairments and restored neurotrophic signaling. This primary hippocampal neuron-corticosterone system offers researchers an efficient platform for mechanistic investigations and preliminary screening of potential antidepressant compounds, potentially facilitating more targeted subsequent in vivo studies while reducing animal usage. By replicating multiple aspects of stress-induced neuronal dysfunction, it represents a valuable tool for depression research and therapeutic development.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150012"},"PeriodicalIF":2.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421221","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 : 2025-10-30DOI: 10.1016/j.brainres.2025.150011
Taís da Silva Teixeira Rech , Mariana Parron Paim , Natalia Gonçalves Tavares , Ila Yasmim Reis Arouche Dantas , José Sebastião Santos Neto , Gabriel da Silva Zani , Silvia de Oliveira Hübner , César Augusto Brüning , Cristiani Folharini Bortolatto
Depression is a psychiatric disorder driven, in part, by neuroinflammation and oxidative stress. Lipopolysaccharide (LPS) induces inflammation, oxidative stress, and cognitive and behavioral alterations in rodents, thereby mimicking depression. It can also trigger peripheral organ damage, such as liver dysfunction, commonly observed in chronic inflammation. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF1) is an antioxidant organoselenium compound with antidepressant-like properties, making it a potential candidate to counteract these effects. This study investigated whether SeBZF1 pretreatment could reduce behavioral and ex vivo alterations in male Swiss mice exposed to LPS. SeBZF1 (50 mg/kg, intragastrically) or fluoxetine (20 mg/kg, intraperitoneally, i.p, positive control) was administered 30 min before LPS (0.83 mg/kg, i.p.), and behavior assessed 24 h later. SeBZF1 significantly reduced LPS‑induced immobility in the tail suspension and forced swim tests and increased grooming in the splash sucrose test, with no changes in locomotion, indicating antidepressant-like and motivational effects. SeBZF1 reduced LPS-induced spatial memory impairment in the Y-maze test. Fluoxetine confirmed the validity of the behavioral tests. Biochemical analyses revealed that SeBZF1 decreased LPS-induced redox imbalance by lowering nitrite/nitrate (plasma), restoring non-protein thiols (prefrontal cortex and hippocampus), and reducing reactive species (hippocampus). SeBZF1 reduced alanine aminotransferase activity, a liver function marker, relative to LPS. Molecularly, SeBZF1-pretreated mice did not exhibit LPS-induced upregulation of nuclear factor kappa B (NFκB), tumor necrosis factor-alpha (TNF-α), or interleukin-4 (IL-4) mRNA in the hippocampus, suggesting anti-inflammatory effects. SeBZF1 also downregulated cortical IL-4 expression. Overall, SeBZF1 demonstrated antidepressant-like, antioxidant, and anti-inflammatory effects, supporting its potential as a candidate for depression associated with neuroinflammation.
{"title":"Antidepressant-like and memory-enhancing effects of 2-phenyl-3-(phenylselanyl)benzofuran on a lipopolysaccharide-induced depression model in male mice: behavioral, biochemical, and molecular insights","authors":"Taís da Silva Teixeira Rech , Mariana Parron Paim , Natalia Gonçalves Tavares , Ila Yasmim Reis Arouche Dantas , José Sebastião Santos Neto , Gabriel da Silva Zani , Silvia de Oliveira Hübner , César Augusto Brüning , Cristiani Folharini Bortolatto","doi":"10.1016/j.brainres.2025.150011","DOIUrl":"10.1016/j.brainres.2025.150011","url":null,"abstract":"<div><div>Depression is a psychiatric disorder driven, in part, by neuroinflammation and oxidative stress. Lipopolysaccharide (LPS) induces inflammation, oxidative stress, and cognitive and behavioral alterations in rodents, thereby mimicking depression. It can also trigger peripheral organ damage, such as liver dysfunction, commonly observed in chronic inflammation. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF<strong>1</strong>) is an antioxidant organoselenium compound with antidepressant-like properties, making it a potential candidate to counteract these effects. This study investigated whether SeBZF<strong>1</strong> pretreatment could reduce behavioral and ex vivo alterations in male Swiss mice exposed to LPS. SeBZF<strong>1</strong> (50 mg/kg, intragastrically) or fluoxetine (20 mg/kg, intraperitoneally, i.p, positive control) was administered 30 min before LPS (0.83 mg/kg, i.p.), and behavior assessed 24 h later. SeBZF<strong>1</strong> significantly reduced LPS‑induced immobility in the tail suspension and forced swim tests and increased grooming in the splash sucrose test, with no changes in locomotion, indicating antidepressant-like and motivational effects. SeBZF<strong>1</strong> reduced LPS-induced spatial memory impairment in the Y-maze test. Fluoxetine confirmed the validity of the behavioral tests. Biochemical analyses revealed that SeBZF<strong>1</strong> decreased LPS-induced redox imbalance by lowering nitrite/nitrate (plasma), restoring non-protein thiols (prefrontal cortex and hippocampus), and reducing reactive species (hippocampus). SeBZF<strong>1</strong> reduced alanine aminotransferase activity, a liver function marker, relative to LPS. Molecularly, SeBZF<strong>1</strong>-pretreated mice did not exhibit LPS-induced upregulation of nuclear factor kappa B (NFκB), tumor necrosis factor-alpha (TNF-α), or interleukin-4 (IL-4) mRNA in the hippocampus, suggesting anti-inflammatory effects. SeBZF<strong>1</strong> also downregulated cortical IL-4 expression. Overall, SeBZF<strong>1</strong> demonstrated antidepressant-like, antioxidant, and anti-inflammatory effects, supporting its potential as a candidate for depression associated with neuroinflammation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150011"},"PeriodicalIF":2.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421147","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 : 2025-10-29DOI: 10.1016/j.brainres.2025.150010
Xiao Cai , Qingfang Zhang
Speech motor control is a complex neuromotor behavior that requires the combined efforts of speech-specific and domain-general brain networks. Over the past decades, multiple studies using the auditory feedback perturbation paradigm or neuropsychological measures have pointed to substantial inter-subject variability in speech motor control. However, the neurocognitive basis underlying such across-subject variability in both normal and disordered speech has rarely been synthesized. In this review, we first analyze the brain structural and functional basis of individualized speech motor control from the perspective of bottom-up auditory-motor processing, emphasizing the importance of neural communication among ‘core’ regions in the frontal-temporal-parietal and basal ganglia-thalamocortical motor networks. We also discuss the brain temporal and frequency basis of this process, identifying N1-P2 complex and high gamma activity as promising neural markers associated with auditory feedback control, while pre-speech auditory modulation and beta-band oscillations are reflective of feedforward control. Finally, we bring together evidence testing the predictive power of speech-specific and domain-general factors, highlighting that this speech-specific network plausibly interacts with the domain-general network, which exerts top-down modulation on stages of auditory error detection and motor correction. Based on prior findings, we summarize the signal flow in speakers’ cortical processing of speech motor control in response to auditory perturbation, providing insights for the neurocognitive basis of inter-subject variability in speech motor control and motor speech disorders.
{"title":"Neurocognitive basis of inter-subject variability in speech motor control: Interaction of bottom-up and top-down processes","authors":"Xiao Cai , Qingfang Zhang","doi":"10.1016/j.brainres.2025.150010","DOIUrl":"10.1016/j.brainres.2025.150010","url":null,"abstract":"<div><div>Speech motor control is a complex neuromotor behavior that requires the combined efforts of speech-specific and domain-general brain networks. Over the past decades, multiple studies using the auditory feedback perturbation paradigm or neuropsychological measures have pointed to substantial inter-subject variability in speech motor control. However, the neurocognitive basis underlying such across-subject variability in both normal and disordered speech has rarely been synthesized. In this review, we first analyze the brain structural and functional basis of individualized speech motor control from the perspective of bottom-up auditory-motor processing, emphasizing the importance of neural communication among ‘core’ regions in the frontal-temporal-parietal and basal ganglia-thalamocortical motor networks. We also discuss the brain temporal and frequency basis of this process, identifying N1-P2 complex and high gamma activity as promising neural markers associated with auditory feedback control, while pre-speech auditory modulation and beta-band oscillations are reflective of feedforward control. Finally, we bring together evidence testing the predictive power of speech-specific and domain-general factors, highlighting that this speech-specific network plausibly interacts with the domain-general network, which exerts top-down modulation on stages of auditory error detection and motor correction. Based on prior findings, we summarize the signal flow in speakers’ cortical processing of speech motor control in response to auditory perturbation, providing insights for the neurocognitive basis of inter-subject variability in speech motor control and motor speech disorders.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1869 ","pages":"Article 150010"},"PeriodicalIF":2.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415495","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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