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Post-mortem 11.7 T DTI validation of myeloarchitectural changes in glioblastoma infiltration: Correlation with histology and PLI 死后11.7 T DTI对胶质母细胞瘤浸润骨髓结构改变的验证:与组织学和PLI的相关性
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-28 DOI: 10.1016/j.brainresbull.2025.111526
Rik van den Elshout , Jenny Schoenmakers , Andor Veltien , Lucas Boer , Benno Küsters , Geert Litjens , Frederick Anton Meijer , Anja van der Kolk , Tom Scheenen , Maximilian Wiesmann , Dylan Henssen
{"title":"Post-mortem 11.7 T DTI validation of myeloarchitectural changes in glioblastoma infiltration: Correlation with histology and PLI","authors":"Rik van den Elshout ,&nbsp;Jenny Schoenmakers ,&nbsp;Andor Veltien ,&nbsp;Lucas Boer ,&nbsp;Benno Küsters ,&nbsp;Geert Litjens ,&nbsp;Frederick Anton Meijer ,&nbsp;Anja van der Kolk ,&nbsp;Tom Scheenen ,&nbsp;Maximilian Wiesmann ,&nbsp;Dylan Henssen","doi":"10.1016/j.brainresbull.2025.111526","DOIUrl":"10.1016/j.brainresbull.2025.111526","url":null,"abstract":"<div><div>Ultra-high field MRI is believed to hold potential for detecting microstructural changes that occur in light of tumor infiltration in glioblastoma patients, although studies with histological validation are lacking. This study, therefore, used 11.7 T diffusion tensor imaging (DTI) to determine the extent of infiltration in post-mortem glioblastoma-affected brain with histological validation. Three post-mortem specimens with glioblastoma underwent 11.7 T DTI from which mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA) were extracted. Tissue samples were also investigated using hematoxylin-eosin (HE) and luxol fast blue (LFB) stains, as well as Polarized Light Imaging (PLI) microscopy. Regions of interest (ROIs) of normal white matter (NWM) and tumor infiltration were generated on HE stain-based nucleus density maps. The metrics of the NWM ROIs were compared to the metrics of the ROIs covering the regions with tumor infiltration. Metrics were subjected to a correlation analysis to assess the correlation between nucleus density data, diffusion-, PLI- and LFB data. Significant differences were found between NWM and regions of tumor infiltration for MD-, RD-, LFB- and PLI-retardance values (p = 0.036, p = 0.010, p = 0.007 and p &lt; 0.001, respectively). A correlation between nucleus density and diffusivity metrics was found, but not with measures for myeloarchitectural changes (LFB and PLI). Also, a significant correlation between PLI-retardance values and LFB values was found (p &lt; 0.001). Based on DTI metrics and histological validation methods, myeloarchitectural alterations (e.g., fiber displacement) were considered the prime driver of measurable changes in the regions of tumor invasion in glioblastoma patients. Although this study shows the potential of ultra-high field MRI in detecting microstructural changes caused by glioblastoma infiltration, future studies are needed to assess these results in the clinical setting.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111526"},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosome derived from bone marrow derived mesenchymal stem cells prevents LPS-induced depressive like behaviors 来自骨髓间充质干细胞的外泌体阻止lps诱导的抑郁样行为。
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-28 DOI: 10.1016/j.brainresbull.2025.111527
Hua Liu , Xue-Jun Yan , Juan-li Hu , Hu Pan , Xiao Mao , Yong Cheng
{"title":"Exosome derived from bone marrow derived mesenchymal stem cells prevents LPS-induced depressive like behaviors","authors":"Hua Liu ,&nbsp;Xue-Jun Yan ,&nbsp;Juan-li Hu ,&nbsp;Hu Pan ,&nbsp;Xiao Mao ,&nbsp;Yong Cheng","doi":"10.1016/j.brainresbull.2025.111527","DOIUrl":"10.1016/j.brainresbull.2025.111527","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a multifaceted mental disorder marked by a spectrum of significant and persistent low mood symptoms. Its etiology involves genetic and environmental factors. In addition, the inflammatory process plays a crucial role in the pathophysiology of depression. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have demonstrated significant effects in reducing proinflammatory cytokines. However, there is limited research on whether exosomes can prevent the occurrence of LPS-induced depression. This study aimed to investigate the role of BMSC-derived exosomes in LPS-induced depression and explore the underlying mechanisms. We administered exosomes to LPS-induced depression mice via the caudal vein and evaluated their effects on depressive-like behaviors. Our findings indicate that four injections of exosomes (200 µl at a concentration of 1.4 ×10 ¹¹ particles/mL, administered every three days) significantly prevented depressive-like behaviors in LPS-induced depression mice. Further analyses revealed that exosome treatment reduced levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory cytokine IL-10. Additionally, exosome treatment markedly reduced oxidative stress in both the central and peripheral nervous systems of LPS-treated mice. Moreover, our data suggest that exosome treatment increased astrocyte proliferation and neurogenesis in the hippocampus of LPS mice. In summary, our results demonstrate the antidepressant effects of BMSC-derived exosomes in LPS-induced depression mice, suggesting a potential new therapeutic target for major depressive disorder (MDD).</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111527"},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trigeminal influences and Locus Coeruleus: Tips for countermeasures, therapies and precocious diagnosis in dementia 三叉神经的影响和蓝斑:痴呆的对策、治疗和早期诊断提示
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-27 DOI: 10.1016/j.brainresbull.2025.111528
Vincenzo De Cicco , Maria Paola Tramonti Fantozzi , Sara Ligori , Enrico Cataldo , Davide De Cicco , Paolo Bongioanni , Cristina Dolciotti , Luca Bruschini , Ugo Faraguna , Diego Manzoni
{"title":"Trigeminal influences and Locus Coeruleus: Tips for countermeasures, therapies and precocious diagnosis in dementia","authors":"Vincenzo De Cicco ,&nbsp;Maria Paola Tramonti Fantozzi ,&nbsp;Sara Ligori ,&nbsp;Enrico Cataldo ,&nbsp;Davide De Cicco ,&nbsp;Paolo Bongioanni ,&nbsp;Cristina Dolciotti ,&nbsp;Luca Bruschini ,&nbsp;Ugo Faraguna ,&nbsp;Diego Manzoni","doi":"10.1016/j.brainresbull.2025.111528","DOIUrl":"10.1016/j.brainresbull.2025.111528","url":null,"abstract":"<div><div>Masticatory dysfunction is a risk factor for Alzheimer ‘s disease (AD), likely due to the trigeminal influences on the Locus Coeruleus (LC), a structure implicated in neurodegenerative processes and whose activity level is reflected by pupil size. Chewing activity acutely stimulates cognitive performance by increasing LC activation during task, as reflected by an increased pupil dilatation (mydriasis). The presence of a trigeminal sensorimotor imbalance is associated to an asymmetry in LC activity (reflected by an asymmetry in pupil size) and is detrimental for performance. These observations prompt for developing testing procedure, in normal elders and in patients affected by AD, aimed to: 1) study the presence of trigeminal asymmetries and to assess the possible contribution of occlusal correction in improving the subject's condition and in preventing/delaying the AD development; 2) verify the stimulating effect of chewing on cognitive performance and task-related mydriasis as an estimate of the LC excitability for determining the subject condition and its susceptibility to undergo AD development. Procedures appropriate for achieving these goals are proposed.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111528"},"PeriodicalIF":3.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mangiferin targets PFKFB3 to inhibit glioblastoma progression by suppressing glycolysis and PI3K/AKT/mTOR signaling 芒果苷靶向PFKFB3,通过抑制糖酵解和PI3K/AKT/mTOR信号传导抑制胶质母细胞瘤进展
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-25 DOI: 10.1016/j.brainresbull.2025.111520
Jiajie Xia , Xiao Li , Jun Yao , Dagang Song , Zhiwei Gu , Gang Zheng , Chuanjian Tu
{"title":"Mangiferin targets PFKFB3 to inhibit glioblastoma progression by suppressing glycolysis and PI3K/AKT/mTOR signaling","authors":"Jiajie Xia ,&nbsp;Xiao Li ,&nbsp;Jun Yao ,&nbsp;Dagang Song ,&nbsp;Zhiwei Gu ,&nbsp;Gang Zheng ,&nbsp;Chuanjian Tu","doi":"10.1016/j.brainresbull.2025.111520","DOIUrl":"10.1016/j.brainresbull.2025.111520","url":null,"abstract":"<div><div>Glioblastoma (GBM) is an aggressive and challenging primary brain tumor with poor prognosis despite advances in surgical resection, radiotherapy, and chemotherapy. Recently, targeting tumor cell metabolic pathways has emerged as a promising strategy for cancer treatment. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a key regulator of glycolysis and is overexpressed in GBM, promoting cell proliferation, migration, and survival. This study aims to evaluate the efficacy of the natural compound mangiferin in inhibiting GBM progression and elucidate its underlying mechanisms. Our screening of a natural compound library identified mangiferin as a potent PFKFB3 inhibitor. In vitro experiments demonstrated that mangiferin significantly inhibited the PI3K/AKT/mTOR signaling pathway by targeting PFKFB3, induced cell cycle arrest in the S phase, and promoted apoptosis in GBM cells. Additionally, mangiferin reduced glycolytic flux, inhibiting cell proliferation and migration. In vivo xenograft mouse models further validated the tumor-suppressive effects of mangiferin, with no observed systemic toxicity. These findings indicate that mangiferin exerts its antitumor effects on GBM by targeting PFKFB3, regulating tumor metabolism and growth. Mangiferin holds promise as a potential therapeutic candidate for the development of targeted therapies against GBM.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111520"},"PeriodicalIF":3.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astrocytes expressing mutant hnRNPA1 induce non-cell-autonomous motor neuron death 表达hnRNPA1突变体的星形胶质细胞诱导非细胞自主运动神经元死亡
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-24 DOI: 10.1016/j.brainresbull.2025.111522
Qinxue Wu , Xionghao Liu , Tingting Zhang , Shiquan Cui , Bo Huang , Cao Huang , Qilin Cao , Xu-Gang Xia , Hongxia Zhou
{"title":"Astrocytes expressing mutant hnRNPA1 induce non-cell-autonomous motor neuron death","authors":"Qinxue Wu ,&nbsp;Xionghao Liu ,&nbsp;Tingting Zhang ,&nbsp;Shiquan Cui ,&nbsp;Bo Huang ,&nbsp;Cao Huang ,&nbsp;Qilin Cao ,&nbsp;Xu-Gang Xia ,&nbsp;Hongxia Zhou","doi":"10.1016/j.brainresbull.2025.111522","DOIUrl":"10.1016/j.brainresbull.2025.111522","url":null,"abstract":"<div><div>Pathogenic mutation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is causative to amyotrophic lateral sclerosis (ALS). Neuron death resulting from pathogenic hnRNPA1 may not require its presence across all pertinent cells types, including neurons, glia, and muscles. Rather, the exclusive presence of pathogenic hnRNPA1 in a specific cell type, such as astrocytes, may suffice to substantially alter cellular functions. Consequently, this alteration initiates abnormal interaction within intricate neuron-glia networks, culminating in non-cell-autonomous motor neuron death. To investigate the pivotal role of non-cell-autonomous neuron death in hnRNPA1-associated ALS, we developed transgenic rats overexpressing mutant hnRNPA1 in specifically astrocytes. The confined overexpression of pathogenic hnRNPA1 in astrocytes instigated a sequence of events resulting in motor neuron death and subsequent muscle atrophy. These findings underscore the critical, non-cell-autonomous contribution of astrocytes to hnRNPA1-induced neurodegeneration in ALS, and point toward astrocytic pathways as potential therapeutic targets.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111522"},"PeriodicalIF":3.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dexmedetomidine attenuates postoperative delirium by activating Nrf2 to reduce oxidative stress and blood-brain barrier disruption 右美托咪定通过激活Nrf2减少氧化应激和血脑屏障破坏来减轻术后谵妄
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-24 DOI: 10.1016/j.brainresbull.2025.111523
Tengchen Feng , Jie Yao , Yanlin Chen , Jiayi Wang , Ying Zhu , Zhiming Lan , Xuhua Huo , Yeming Wang , Jingui Gao
{"title":"Dexmedetomidine attenuates postoperative delirium by activating Nrf2 to reduce oxidative stress and blood-brain barrier disruption","authors":"Tengchen Feng ,&nbsp;Jie Yao ,&nbsp;Yanlin Chen ,&nbsp;Jiayi Wang ,&nbsp;Ying Zhu ,&nbsp;Zhiming Lan ,&nbsp;Xuhua Huo ,&nbsp;Yeming Wang ,&nbsp;Jingui Gao","doi":"10.1016/j.brainresbull.2025.111523","DOIUrl":"10.1016/j.brainresbull.2025.111523","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative delirium (POD), characterized by cognitive dysfunction, is a prevalent and severe complication following surgery. The blood-brain barrier (BBB) is crucial in maintaining central nervous system (CNS) homeostasis, and its disruption is associated with POD. Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, potentially reduces POD incidence by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which regulates antioxidant responses and alleviates BBB damage.</div></div><div><h3>Methods</h3><div>This study used transcriptomic analysis to identify differentially expressed genes in patients with POD and explored the therapeutic targets of DEX. <em>In vitro</em> experiments using HCMEC/D3 cells and an <em>in vivo</em> mouse model of POD were conducted to assess the effects of DEX on BBB integrity and neuroinflammation. Western blotting, flow cytometry, and ELISA were used to evaluate protein expression, apoptosis, and cytokine levels, respectively. Behavioral tests (open-field and Y-maze tests) were performed to assess cognitive function in mice.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed Nrf2 as a key target of DEX. DEX treatment significantly increased Nrf2 expression and alleviated oxidative stress and neuroinflammation in HCMEC/D3 cells. In the POD mouse model, DEX improved cognitive function, evidenced by enhanced performance in behavioral tests. DEX also upregulated Nrf2 expression in the mouse brain tissue and reduced serum inflammatory. Furthermore, DEX preserved BBB integrity by upregulating tight junction proteins, which was reversed by the Nrf2 inhibitor, ML385.</div></div><div><h3>Conclusions</h3><div>DEX ameliorates POD by activating Nrf2, thereby reducing oxidative stress and inflammation, and maintaining BBB integrity. These findings suggest DEX is a potential therapeutic agent for POD, highlighting the Nrf2 pathway as a novel target for treatment strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111523"},"PeriodicalIF":3.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Electroacupuncture reduces microglial hyperactivity and synaptic phagocytosis in the medial prefrontal cortex to treat chronic pain comorbid with anxiety and depression 电针减少内侧前额皮质小胶质细胞亢进和突触吞噬治疗伴焦虑和抑郁的慢性疼痛。
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-23 DOI: 10.1016/j.brainresbull.2025.111521
Wei Li , Weiqi Chang , Kaiyu Cui , Zuqi Shen , Xuan Yin , Shifen Xu
{"title":"Electroacupuncture reduces microglial hyperactivity and synaptic phagocytosis in the medial prefrontal cortex to treat chronic pain comorbid with anxiety and depression","authors":"Wei Li ,&nbsp;Weiqi Chang ,&nbsp;Kaiyu Cui ,&nbsp;Zuqi Shen ,&nbsp;Xuan Yin ,&nbsp;Shifen Xu","doi":"10.1016/j.brainresbull.2025.111521","DOIUrl":"10.1016/j.brainresbull.2025.111521","url":null,"abstract":"<div><div>The role of dysfunctional microglial phagocytosis in the comorbidity of pain and affective disorders remains unclear. This study aimed to develop a potential therapeutic strategy targeting microglial phagocytosis. We established a mouse model of chronic constriction injury of the infraorbital nerve (CION) to induce pain and anxiety- and depressive-like behaviors simultaneously. Immunohistochemical analysis showed that CION led to increased density and aberrant morphology of microglia in the medial prefrontal cortex (mPFC), upregulation of lysosome-associated membrane protein 2 (LAMP2) and MER proto-oncogene tyrosine kinase (MERTK), and significant enhancement of phagocytosis of PSD-95-positive synaptic components by microglia. However, local injection of the microglia inhibitor minocycline into the mPFC markedly alleviated pain-induced anxiety-like behaviors. As a non-pharmacological intervention, electroacupuncture (EA) reduced the severity of pain-induced anxiety- and depressive-like behaviors, decreased the density of microglia and restored their morphology in the mPFC, and normalized MERTK expression levels. These results suggest that aberrant phagocytosis of excitatory synapses by microglia in the mPFC participates in regulating pain-induced anxiety-like behaviors, likely through MERTK. Pharmacological and non-pharmacological approaches (e.g., EA) targeting microglial phagocytosis in the mPFC may represent novel therapeutic strategies for chronic pain comorbid with anxiety and depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111521"},"PeriodicalIF":3.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of DYRK1A can alleviate MPTP/MPP+-induced neuronal apoptosis and mitochondrial damage 抑制DYRK1A可减轻MPTP/MPP+诱导的神经元凋亡和线粒体损伤
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-22 DOI: 10.1016/j.brainresbull.2025.111516
Qian Cai , Huan Xia , Peishan Li , Yani Yao , Qin Luo , Xinling Yang
{"title":"Inhibition of DYRK1A can alleviate MPTP/MPP+-induced neuronal apoptosis and mitochondrial damage","authors":"Qian Cai ,&nbsp;Huan Xia ,&nbsp;Peishan Li ,&nbsp;Yani Yao ,&nbsp;Qin Luo ,&nbsp;Xinling Yang","doi":"10.1016/j.brainresbull.2025.111516","DOIUrl":"10.1016/j.brainresbull.2025.111516","url":null,"abstract":"<div><div>The dual specificity tyrosine-regulated kinase 1a (DYRK1A) gene plays a crucial role in developing midbrain dopamine neurons. DYRK1A is closely related to Parkinson's disease(PD), and there are not many relevant studies. This paper focuses on the potential role of DYRK1A in the initiation and progression of PD and the discovery of therapeutic targets for PD. 94 PD patients and healthy controls were included as research subjects, and the levels of DYRK1A, α-synuclein(α-syn), phosphorylated α-synuclein(p-α-syn) in plasma and α-syn, p-α-syn in erythrocytes were detected by ELISA. Differences in plasma DYRK1A between the PD group and the control group and the relevant influencing factors of plasma DYRK1A in the PD group were statistically analyzed. Different concentrations of Harmine, a DYRK1A inhibitor, were added to the mouse model of PD and DYRK1A was knocked down in MN9D cells to investigate changes in animal behavior, neuronal apoptosis, mitochondrial damage and autophagy after inhibition of DYRK1A expression. We found that plasma DYRK1A was elevated in PD patients and correlated with plasma α-syn, p-α-syn, and erythrocyte α-syn and p-α-syn levels. Expression of DYRK1A was upregulated in the animal model and cellular model, and the DYRK1A inhibitor ameliorated behavioral deficits and attenuated neuronal apoptosis; knockdown of DYRK1A attenuated apoptosis, whereas overexpression of DYRK1A exacerbated apoptosis. Furthermore, we also found that DYRK1A inhibitor or knockdown of DYRK1A can reduce mitochondrial damage and promote autophagy. Inhibition of DYRK1A may be a future target for treating PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111516"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A behavioural assay for investigating cued conflict between allocentric and egocentric spatial memory with instinctive escape in mice 研究小鼠异中心与自我中心空间记忆本能逃避提示冲突的行为实验。
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-18 DOI: 10.1016/j.brainresbull.2025.111515
Kendall D. Mar , Chanbee So , Jun Chul Kim
{"title":"A behavioural assay for investigating cued conflict between allocentric and egocentric spatial memory with instinctive escape in mice","authors":"Kendall D. Mar ,&nbsp;Chanbee So ,&nbsp;Jun Chul Kim","doi":"10.1016/j.brainresbull.2025.111515","DOIUrl":"10.1016/j.brainresbull.2025.111515","url":null,"abstract":"<div><div>Instinctive escape behavior is widely recognized as a reliable model for assessing spatial memory in mice. Here, we present a novel behavioral assay designed to evaluate how mice navigate toward a learned goal relying on a variable proximal LED landmark or internal egocentric cues to provide spatial orientation in the absence of distal cues. Escape to a learned shelter was triggered by an innately aversive auditory stimulus in the presence of a proximal LED landmark. To assess cue preference (egocentric vs. allocentric), we introduced a cue-conflict situation where the allocentric LED cue was deliberately shifted away from the previously visited shelter location. In a no-conflict scenario, the LED stayed directly above the shelter. Baseline tests in C57BL/6 J mice showed a decreased reliance on allocentric cues as the LED landmark deviated further from the actual shelter. When the disparity between the LED cue and the shelter location exceeded a threshold, the mice began to favor egocentric strategies over allocentric ones. To demonstrate its utility, we applied the cue-conflict assay in a cross-sectional study of the 5xFAD Alzheimer's disease (AD) mouse model at early pathological stages (2–3 months of age). Escape profiles in AD and wild-type (WT) mice revealed a complex, genotype-dependent pattern of behavior across LED shift conditions, independent of disease progression. Although both AD and WT mice exhibited a higher incidence of allocentric (LED-directed) escapes when the LED shift was small, our analysis did not reveal significant changes in escape strategy that were associated with condition, genotype or age. Future studies using neural recording and manipulation techniques can further elucidate the circuit-level mechanisms underlying the cue conflict resolution.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111515"},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice 成年C57BL/6 J小鼠全脑丝氨酸结合子2mrna的空间分布
IF 3.7 3区 医学
Brain Research Bulletin Pub Date : 2025-08-18 DOI: 10.1016/j.brainresbull.2025.111519
Tianlang Ke , Ruilan Yang , Zewen Tan , Liping Cao , Xuemei Liu
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