Brain Research最新文献

{"title":"Neurotoxic significance of H₂O₂ generation in nigral dopaminergic damage by paraquat and protective action of effusol and dehydroeffusol, Juncus effusus ingredients.","authors":"Haruna Tamura, Haruna Tamano, Toshiyuki Fukuda, Yasuhito Akagi, Shinji Ikeura, Atsushi Takeda","doi":"10.1016/j.brainres.2025.149869","DOIUrl":"10.1016/j.brainres.2025.149869","url":null,"abstract":"<p><p>H₂O₂ generation by paraquat (PQ) leads to accumulating glutamate in the nigral extracellular compartment and then excessive influx of extracellular Zn²⁺ by AMPA receptor activation, resulting in dopaminergic cell death. Here we tested a postulation that the strategy for inactivating H₂O₂ generation by PQ protects dopaminergic neurons. Either HYDROP for capturing intracellular H₂O₂ or HYDROP-EX for capturing extracellular H₂O₂ was co-injected with PQ into the rat substantia nigra pars compacta (SNpc) and dopaminergic damage was determined by tyrosine hydroxylase (TH) immunostaining. The decrease in SNpc TH stain was avoided by co-injection. The effect of HYDROP-EX supports the previous evidence that intracellular H₂O₂ generated by PQ through dopamine transporters is transported to the extracellular compartment and linked with the decrease in TH stain. Furthermore, we tested the effect of effusol and dehydroeffusol, unique phenanthrene ingredients in Juncus effusus. The decrease in SNpc TH stain was also avoided in the presence of effusol or dehydroeffusol. Effusol suppressed both PQ-induced accumulations of extracellular glutamate and intracellular H₂O₂. In contrast, dehydroeffusol did not suppress accumulation of extracellular glutamate, but suppressed accumulation of intracellular H₂O₂. This paper first indicates neurotoxic significance of PQ-mediated H₂O₂ generation at nigral glutamatergic-dopaminergic synapses. Effusol and dehydroeffusol may protect dopaminergic neurons via reducing H₂O₂ generation by PQ.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149869"},"PeriodicalIF":2.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From particulates to pathways: environmental exposures and their impact on Alzheimer's disease.","authors":"Bing Liu, Muhammad Arslan Ahmad, Ghulam Abbas, Usama Ahmed, Rabia Javed, Ilyas Ali, Qiang Ao, Xu Deng","doi":"10.1016/j.brainres.2025.149880","DOIUrl":"10.1016/j.brainres.2025.149880","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a leading cause of cognitive decline and mortality, with its neurobiological mechanisms and etiology still not fully understood. Emerging evidence highlights the significant role of environmental pollutants in AD onset and progression. This review examines the impact of environmental compartments-air, water, soil, and pollutants-on AD pathology. Prolonged exposure to particulate matter (PM_2.5), heavy metals (lead, cadmium, mercury, arsenic), and engineered nanomaterials (silver, iron oxide, silica) increases AD risk. Additional factors like obesity, smoking, infections, cardiovascular diseases, diabetes, and electromagnetic fields may exacerbate AD. These exposures potentially drive key pathological features such as amyloid-β plaque deposition and tau protein aggregation. By analyzing recent studies, this review highlights the intersection between environmental exposure and AD progression, emphasizing how such factors can accelerate the disease. It provides practical guidelines to mitigate these risks, aiming to reduce AD incidence while advancing understanding of its environmental contributions.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149880"},"PeriodicalIF":2.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal transcranial direct current stimulation enhances the analgesic effects of attention bias modification: a randomized controlled trial.","authors":"Xue Jiang, Haozhi Zhao, Ruihan Wan, Chen Gong, Beibei Feng, Yafei Wang, Yangfan Xu, Wangwang Yan, Xueqiang Wang, Yixuan Ku, Yuling Wang","doi":"10.1016/j.brainres.2025.149976","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149976","url":null,"abstract":"<p><p>This study aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) augmented the effect of attentional bias modification (ABM) on pain perception and to explore the potential neuroimaging mechanism by functional infrared spectroscopy (fNIRS). This randomized, single-blind, and parallel-controlled trial enrolled 46 healthy volunteers who were then randomly assigned to two groups, namely active HD-tDCS combined with ABM and sham HD-tDCS combined with ABM groups. The pressure pain threshold (PPT), cold pain threshold, cold pain tolerance, pain intensity, pain unpleasantness, and attentional bias were measured before and after the intervention. fNIRS was used to monitor cerebral hemodynamic responses during repeated cold pain stimulation tasks. Compared to the sham group, the active HD-tDCS plus ABM group demonstrated significantly greater improvements in PPT. Mixed-design ANOVA revealed significant Time × Group interactions for PPT at both the forearm and leg sites. Simple effects analyses showed that PPT significantly increased from pre- to post-intervention in the active group (forearm: p < 0.001; leg: p < 0.001), whereas no significant change was observed in the sham group for the forearm (p = 0.597) and only a small increase was observed at the leg site (p = 0.036). Between-group differences at post-intervention were not significant. Cold pain unpleasantness ratings also demonstrated a significant Time × Group interaction (p = 0.011), with decreases in the active group (p < 0.001) but not in the sham group (p = 0.305); at post-intervention, the active group reported lower unpleasantness than the sham group (p = 0.025). No significant group or interaction effects were observed for cold pain threshold, cold pain tolerance, pain intensity, or attentional bias. Our findings showed that active HD-tDCS combined with ABM training enhanced the analgesic effect of ABM training and reduced pain unpleasantness rating. The analgesic effect may be associated with changes in the activation of prefrontal cortex. However, this effect may not be mediated by modifying the direction of pain attention bias. Further experiments are needed to clarify the analgesic effect of HD-tDCS combined with ABM training on those with clinical pain.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149976"},"PeriodicalIF":2.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease and the gut-brain connection: unveiling pathways, mechanisms and promising therapies.","authors":"Suhas Hajare, Yogesh A Kulkarni","doi":"10.1016/j.brainres.2025.149975","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149975","url":null,"abstract":"<p><p>Parkinson's disease is the second most common neurodegenerative disorder, with a global prevalence of over 6.1 million in 2016, a figure expected to rise with an ageing population. According to recent research findings, the gut-brain axis plays a crucial role in understanding the development of Parkinson's Disease. The Gut-Brain axis establishes communication pathways between gut microbiota, the enteric nervous system, and the CNS through neural, immune and endocrine signals. The gut microbiota regulates neuroinflammatory response, neurotransmitter transmissions and motor dysfunction through its production of short-chain fatty acids, neurotransmitters, and immune system control mechanisms. Through the vagus nerve, the Enteric nervous system links the brain and gut to earning it the designation of the \"second brain\". Alterations in gut microbiota in PD patients result in increased intestinal permeability, permitting bacterial endotoxins such as lipopolysaccharides to enter the bloodstream and trigger systemic inflammation. This subsequently stimulates microglia and astrocytes in the brain, intensifying neuroinflammation and dopaminergic neuronal degeneration. Furthermore, α-synuclein aggregates originating from the gut transmit to the brain through the vagus nerve, employing a prion-like mechanism that promotes Lewy body pathology. Recent research suggests that probiotics, natural products, and synthetic drugs may restore microbial homeostasis, enhance gut barrier integrity, and modulate neuroinflammatory responses, offering potential therapeutic benefits for Parkinson's disease. Probiotics have been shown to reduce inflammation, improve gut motility, and mitigate α-synuclein pathology. This review underscores the bidirectional interplay between gut and brain, highlighting the potential of gut-centric therapies in mitigating PD pathology and improving patient outcomes.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149975"},"PeriodicalIF":2.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-mediated mechanisms of cognitive memory dysfunction: From autoimmune diseases to therapeutic neuromodulation.","authors":"Limor Shtoots, Gilad Halpert, Roni Partouche, Daniel A Levy, Howard Amital, Yehuda Shoenfeld","doi":"10.1016/j.brainres.2025.149980","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149980","url":null,"abstract":"<p><p>Cognitive memory is fundamental to how humans adapt, form identity, and retain experiences. Recent research highlights that memory processes are modulated by the immune system. Here, we review both preclinical and clinical findings to examine how dysregulated immunity impairs memory processes. This review discusses broad immune-memory dynamics to disease-specific disruptions in autoimmune disorders, including intervention strategies aimed at mitigating immune-related cognitive dysfunction. We emphasize the roles of cytokines, autoantibodies, and neuroinflammation in affecting memory-related brain regions. Infectious diseases are also discussed as potential triggers and modulators of immune-mediated cognitive impairment, expanding the scope of relevant etiological factors. Addressing these specific pathways could offer more targeted therapeutic opportunities for cognitive deficits in immune-mediated conditions. Autoimmune diseases such as systemic lupus erythematosus (SLE), autoimmune encephalitis (AE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) are examined, with attention to studies that disentangle memory impairments from comorbid factors like depression and fatigue. In addition to neurological autoimmune syndromes, we also review psychiatric autoimmune syndromes, emphasizing their shared impact on memory dysfunction. Additionally, Fibromyalgia (FM), increasingly conceptualized as having autoimmune features, is discussed as a chronic pain syndrome with emphasis on its cognitive dysfunction aspects. Memory deficits are frequently reported in FM, suggesting immune-mediated disruption of higher-order cognitive processes. Finally, we explore emerging non-invasive neuromodulation techniques, including transcranial Direct Current Stimulation (tDCS), and transcranial Alternating Current Stimulation (tACS), as tools for restoring cognitive function in FM.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149980"},"PeriodicalIF":2.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations for quantifying brain asymmetry using neuroimaging techniques","authors":"Haokun Li ,&nbsp;Jingli Qu ,&nbsp;Gaolang Gong","doi":"10.1016/j.brainres.2025.149979","DOIUrl":"10.1016/j.brainres.2025.149979","url":null,"abstract":"<div><div>Structural and functional asymmetries are crucial for understanding the relationship between the left and right hemispheres of the human brain. Quantifying brain asymmetry or lateralization represents a fundamental methodological choice in this field, and approaches vary considerably across studies. This review aims to briefly summarize and discuss methodological considerations for quantifying brain asymmetry across different neuroimaging techniques and research contexts. We illustrate how the definition of specific homotopic units serves as a prerequisite, how the degree of hemispheric asymmetry between these units is quantified using lateralization index formulas, and how the application of these lateralization indices requires careful consideration.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149979"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations for quantifying brain asymmetry using neuroimaging techniques","authors":"Haokun Li ,&nbsp;Jingli Qu ,&nbsp;Gaolang Gong","doi":"10.1016/j.brainres.2025.149979","DOIUrl":"10.1016/j.brainres.2025.149979","url":null,"abstract":"<div><div>Structural and functional asymmetries are crucial for understanding the relationship between the left and right hemispheres of the human brain. Quantifying brain asymmetry or lateralization represents a fundamental methodological choice in this field, and approaches vary considerably across studies. This review aims to briefly summarize and discuss methodological considerations for quantifying brain asymmetry across different neuroimaging techniques and research contexts. We illustrate how the definition of specific homotopic units serves as a prerequisite, how the degree of hemispheric asymmetry between these units is quantified using lateralization index formulas, and how the application of these lateralization indices requires careful consideration.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149979"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent high-fructose corn syrup consumption contributes to protracted dysregulation of adult accumbal neuroinflammation and affective behaviors.","authors":"Jessica L Santerre-Anderson, Maritza Colon, Brynn Pike, Corinne Kiessling","doi":"10.1016/j.brainres.2025.149978","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149978","url":null,"abstract":"<p><p>Adolescence is an important period of neurodevelopment often accompanied by escalated consumption of added sweeteners, such as high fructose corn syrup (HFCS). Data from our lab suggests that overconsumption of HFCS during adolescence contributes to deficits in learning and motivation, as well as increases in depression which persists in adulthood. The present study aimed to assess whether neuroinflammation contributed to persistent changes in affective behaviors following adolescent HFCS overconsumption. Males but not female Sprague-Dawley rats exposed to HFCS during the adolescent period, exhibited dysregulation of both accumbal C-Reactive protein and Interleukin-6 in adulthood. Further, alterations in neuroinflammatory proteins were observed at earlier timepoints while HFCS was still being administered. Behaviorally, pharmacological inhibition of neuroinflammation by minocycline occluded HFCS-dependent increases in immobility time on a forced swim paradigm but was unable to circumvent increases in open-arm time on an elevated plus maze. Taken together, these data suggest that adolescent HFCS-overconsumption contributes to dysregulation of accumbal neuroinflammatory proteins. Further, neuroinflammation may underlie alterations in affective behaviors which persist following cessation of HFCS-exposure.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149978"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infra-slow frequency oscillations propagating through multiple organs convey information on phase-specific timing for self-initiated actions.","authors":"Filip Spaniel, Jiri Anyz, Dominika Grygarova, Jan Hubeny, Vlastimil Koudelka, Ilia Shalkin, Jan Strobl, Jaroslav Hlinka, Tomas Nagy, Lea Jakob, Jakub Schneider, Jan Kudelka, Eduard Bakstein","doi":"10.1016/j.brainres.2025.149964","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149964","url":null,"abstract":"<p><p>Cognitive functions crucial for voluntary actions fluctuate with infra-slow frequencies (ISF, <0,2 Hz), indicating their potential impact with self-driven behavior. ISF's involvement in brain-body interaction suggests that the link between ISF oscillations and self-initiated actions can be explored through low-frequency physiological readouts in peripheral organs. Based on these insights, we investigated if ISF in peripheral systems relates to spontaneous motor activity. We analyzed pupillary hippus, heart RR intervals, and respiration against self-paced button presses across various ISF frequencies in 16 participants. Our results were validated with a second dataset of 25 healthy individuals. Self-initiated actions were more likely to occur within a specific phase of the slow3 ISF band (0.073-0.198 Hz) across all observed organ systems. We found phase-locking in the slow3 across those physiological signals, indicating synchronized ISF oscillations spreading throughout the body. The phase locking of spontaneous actions is not distributed randomly. At certain phases of ISF slow3 oscillations, self-initiated actions prevail. This suggests that determined ISF oscillations detectable in the autonomic nervous system relate to when we act. Further exploration of this pathway could deepen insights into the complexities of conscious action initiation. The study did not measure the timing or presence of conscious intention and therefore cannot determine whether conscious will is the final trigger for action.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149964"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanoparticles reduce ischemic brain injury in rats by activating autophagy and inhibiting apoptosis","authors":"Xuejing Ma,&nbsp;Chang Liu,&nbsp;Yanyan Yang,&nbsp;Lili Ren,&nbsp;Yunhao Xu,&nbsp;Jiachen Li,&nbsp;Peng Wang","doi":"10.1016/j.brainres.2025.149974","DOIUrl":"10.1016/j.brainres.2025.149974","url":null,"abstract":"<div><div>Ischemic stroke, the main type of stroke, is the leading cause of human death and disability worldwide. This study aims to investigate the effect of gold nanoparticles (Au-NPs) on cerebral ischemia/reperfusion (I/R) injury in rats. Au-NPs was prepared by trisodium citrate reduction method. Transient middle cerebral artery occlusion/reperfusion (tMCAO) was used to mimic cerebral ischemia. Behavioral tests, 2,3,5-triphenyl tetrazolium chloride staining, Hematoxylin &amp; Eosin staining, Nissl staining and TUNEL staining, were performed to evaluate cerebral injury following tMCAO. Brain tissues were collected and analyzed for ERK activation, autophagy, and apoptosis. The particle size of the prepared Au-NPs was about 15 nm, and the distribution was regular and uniform. Au-NPs treatment improved neurological outcomes and reduced infarct volume. Furthermore, Au-NPs treatment<!--> <!-->alleviated tMCAO induced apoptosis in rats and increased autophagy. In addition, Au-NPs treatment activated the ERK and ERK inhibitor PD98059 reversed the neuroprotective effects of Au-NPs on ischemic stroke injury.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149974"},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211581","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}