Brain Research最新文献

Corrigendum to “Sensitivity and reliability of fNIRS to detect cochlear implant-induced auditory cortical activation in prelingually deaf children with inner ear malformation or cochlear nerve deficiency” [Brain Res. 1856 (2025) 149578]

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-09 DOI: 10.1016/j.brainres.2025.149615

Hiroshi Yamazaki , Saburo Moroto , Tomoko Yamazaki , Rinko Tamaya , Naoko Fujii , Keizo Fujiwara , Yasushi Naito

引用次数: 0

Collaborative multitasking framework for enhanced hippocampus segmentation and Alzheimer’s disease classification

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-07 DOI: 10.1016/j.brainres.2025.149610

Lingling Fang, Xin Fu, Yongcheng Yu, Deshan Liu

The early diagnosis of Alzheimer’s disease has faced significant challenges, as the initial patients have hidden symptoms that are difficult to distinguish from conventional symptoms. In view of this, this article designs a collaborative multitasking algorithm framework that implements a positive feedback loop between classification tasks, significantly improving processing accuracy. Specifically, the algorithm consists of three sub networks: the initial segmentation sub network accurately identifies the hippocampus boundary and generates the initial segmentation mask; The classification subnetwork relies on initial segmentation information to effectively distinguish different stages of Alzheimer’s disease; Finally, the fine segmentation sub network finely adjusts the contour of the hippocampus based on the classification results. To verify the superiority of this method, this study used 269 MRI sample of Alzheimer’s disease patients, including clinical and public datasets. The experimental results demonstrate that the proposed method exhibits superior performance in both hippocampal classification and segmentation tasks. Specifically, in terms of segmentation, the method achieved an average Dice Similarity Coefficient (DSC) of 94.0% and a Jaccard Index (JA) of 80.6%. For classification tasks, the method demonstrated an accuracy (AC) of 98.8%, sensitivity (SEN) of 98.8%, specificity (SP) of 98.6%, and F1 score (F1) of 97.8%, collectively indicating excellent clinical performance.

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引用次数: 0

An enriched environment restored hippocampal cell patterns and enhanced short-term memory in gestational and breastfeeding protein-restricted male offspring. 丰富的环境可恢复妊娠期和母乳喂养蛋白质受限的雄性后代的海马细胞模式并增强其短期记忆。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-04 DOI: 10.1016/j.brainres.2025.149598

Gabriel Boer Grigoletti-Lima, Patrícia Aline Boer, José Antonio Rocha Gontijo

Maternal undernutrition impacts neuron proliferation and differentiation, non-neuron onset, and cell migration, leading to changes in long-term offspring's brain morphology and functionality. This study evaluated the effect of maternal protein intake restriction and enriched environment on the structural hippocampus and behavioral tests in 42-day-old male (low-protein) LP compared to NP (control) offspring. The study supports the selfish brain theory, which suggests that the brain maintains its mass despite significant changes in body weight. The hippocampus cellularity pattern was profoundly altered by reduced neuron numbers in the LP compared to the age-matched NP progeny, as revealed by the isotropic fractionation technique. Detailed data analysis revealed a discrepancy between behavioral tests and reduced hippocampal stem cells and neuron number, accompanied by increased non-neuronal cells, linked to a significant decrease in fear-reflecting behavior. However, the enriched environment (EE) was found to restore the altered neuronal hippocampi cellularity significantly and modify the discrimination ratio, enhancing the ability of both progenies to discriminate between novel and familiar objects in a short time, potentially associated with reversing abnormal hippocampus cell patterns. Immunohistochemistry further validated these findings, showing reduced progenitor cells, neurons and total cells in mitosis in the LP offspring. At the same time, the enriched environment significantly increased hippocampal cell proliferation, a promising result that could lead to the recovery of neuronal stem cell numbers. The present data underscore the detrimental impact of gestational protein restriction on brain development and highlight EE's potential to restore altered neuronal hippocampi cellularity, offering a hopeful outlook for future research and interventions.

母体营养不良会影响神经元的增殖和分化、非神经元的发生以及细胞迁移，从而导致长期后代的大脑形态和功能发生变化。本研究评估了母体蛋白质摄入限制和丰富环境对42天大雄性（低蛋白）LP与NP（对照组）后代海马结构和行为测试的影响。该研究支持 "自私大脑 "理论，即尽管体重发生了显著变化，大脑仍能保持其质量。各向同性分馏技术显示，与年龄匹配的 NP 后代相比，LP 后代的神经元数量减少，从而严重改变了海马的细胞形态。详细的数据分析显示，行为测试与海马干细胞和神经元数量的减少以及非神经元细胞的增加之间存在差异，这与恐惧反射行为的显著减少有关。然而，研究发现，富集环境（EE）能显著恢复改变了的海马神经细胞，并改变辨别比率，在短时间内提高两种后代辨别新事物和熟悉事物的能力，这可能与逆转异常海马细胞模式有关。免疫组化进一步验证了这些发现，结果显示，LP后代的祖细胞、神经元和有丝分裂中的细胞总数均有所减少。与此同时，富集环境显著增加了海马细胞的增殖，这一令人鼓舞的结果可能导致神经元干细胞数量的恢复。本数据强调了妊娠蛋白质限制对大脑发育的不利影响，并突出了EE恢复已改变的神经元海马细胞的潜力，为未来的研究和干预提供了一个充满希望的前景。

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引用次数: 0

Alterations in NFAT5 and ATP6V1E1 expression as potential diagnostic biomarkers in blood and brain for Alzheimer's disease: A study of gene overlap.

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-03 DOI: 10.1016/j.brainres.2025.149599

Farnoosh Akbari, Roksana Soheilian, Samin Tavalaeian, Atefeh Zamani, Mohammad Mahdevar

Introduction: Alzheimer's disease (AD), a prevalent cause of dementia, is characterized by amyloid plaques and tau tangles. It requires early diagnosis through blood markers. This study examined changes in gene expression in blood and brain samples from patients with AD as potential diagnostic biomarkers.

Methods: The study utilized gene expression data from public studies, including GSE4757, GSE5281, GSE28146, GSE48350, and GSE63060, to investigate expression changes in AD. Data integration and differential expression analysis were performed, and pathways related to candidate genes were identified using the Enrichr and BioPlents databases. Blood samples from 50 AD and controls were collected, followed by RNA extraction, cDNA synthesis, and qRT-PCR analysis using specific NFAT5 and ATP6V1E1 gene primers RESULTS: We found 394 genes with increased expression and 759 with decreased expression in brain tissue. Upregulated genes were linked to TGF-B, BDNF, apoptosis, Hippo, P53, and IL-2 and IL-4 pathways. In contrast, downregulated genes were associated with pathways related to oxidative phosphorylation, PGC1-A, GABA, Alzheimer's, and calcium. Blood expression data showed 1147 probes with increased expression and 1413 with significant decreases. We found 31 genes that were upregulated and 87 genes that were downregulated, consistent across both blood and brain samples. Among the overlapping genes, RT-qPCR results indicated that the expression levels of NFAT5 and ATP6V1E1 may have diagnostic potential in the blood samples of Alzheimer's patients.

Conclusion: The study identified changes in gene expression related to Alzheimer's in blood and brain samples. These changes affect pathways such as IL-2 and oxidative phosphorylation. Both in silico and ex vivo results revealed that the expression levels of NFAT5 and ATP6V1E1 in blood samples can serve as potential diagnostic biomarkers for Alzheimer's patients.

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引用次数: 0

From encoding to recognition: Exploring the shared neural signatures of visual memory

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-03 DOI: 10.1016/j.brainres.2025.149616

Berfin Ozdemir, Géza Gergely Ambrus

This study investigated the shared neural dynamics underlying encoding and recognition processes across diverse visual object stimulus types in short term experimental familiarization, using EEG-based representational similarity analysis and multivariate cross-classification. Building upon previous research, we extended our exploration to the encoding phase. We show early visual stimulus category effects around 150 ms post-stimulus onset and old/new effects around 400 to 600 ms. Notably, a divergence in neural responses for encoding, old, and new stimuli emerged around 300 ms, with items encountered during the study phase showing the highest differentiation from old items during the test phase. Cross-category classification demonstrated discernible memory-related effects as early as 150 ms. Anterior regions of interest, particularly in the right hemisphere, did not exhibit differentiation between experimental phases or between study and new items, hinting at similar processing for items first encountered, irrespective of experiment phase. While short-term experimental familiarity did not consistently adhere to the old >new pattern observed in long-term personal familiarity, statistically significant effects are observed specifically for experimentally familiarized faces, suggesting a potential unique phenomenon specific to facial stimuli. Further investigation is warranted to elucidate underlying mechanisms and determine the extent of face-specific effects. Lastly, our findings underscore the utility of multivariate cross-classification and cross-dataset classification as promising tools for probing abstraction and shared neural signatures of cognitive processing.

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引用次数: 0

Shared and unique genes and pathways between neuropathic and inflammatory pain assays

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-03 DOI: 10.1016/j.brainres.2025.149614

Shuxian Wang , Lingji Zhou , Weiyu Pu , Jiajia Dai , Song Cao

Background

Current studies mostly concentrate on behavioral differences and have not yet systematically elucidated the molecular distinctions among various chronic pain models.

Methods

To identify the similarities and differences in gene expression among mice of three kinds of pain models, i.e., spared nerve injury (SNI) model, chronic constriction injury of the sciatic nerve (CCI) model, and the complete Freund’s adjuvant-induced chronic inflammatory pain (CFA) model. The lumbar enlargement segments (L5-L6) were collected. Total mRNA was extracted for RNA sequencing. The differentially expressed genes were analyzed by bioinformatics, including GO analysis, KEGG analysis, and PPI network to explore the functions.

Results

Commonalities and significant variations in gene expression were observed among the three pain models. Compared with Sham, there were 60 shared differential genes among the three models, which were mainly involved in oxidative phosphorylation-related biological process (e.g., mt-Nd1). Compared with CCI, SNI upregulated genes were associated with inflammation response (e.g., Ifi204, Ifi27), while downregulated genes were linked to microtubule-based movement (e.g., Dnah7b, Hcmn1); When compared with SNI, CFA upregulated genes were related to axon development (e. g., Oprm1, Gucy1a2, Syn3), whereas downregulated genes were associated with oxidative phosphorylation (e. g., Rpl41, Rpl21); In contrast to CCI, CFA upregulated genes pertained to axon development (e. g., Zbtb16), while downregulated genes were connected to oxidative phosphorylation (e. g., Cyp3a13).

Conclusions

The three widely employed chronic pain models exhibit both similarities and distinctions, and genes that vary across all three models may serve as potential targets for chronic pain research.

背景：目前的研究大多集中在行为差异上，尚未系统地阐明各种慢性疼痛模型的分子差异：目前的研究大多集中在行为差异上，尚未系统阐明各种慢性疼痛模型之间的分子差异：方法：确定神经损伤（SNI）模型、坐骨神经慢性收缩损伤（CCI）模型和完全弗氏佐剂诱导的慢性炎症性疼痛（CFA）模型三种疼痛模型小鼠基因表达的异同。收集腰椎扩大节段（L5-L6）。提取总 mRNA 进行 RNA 测序。对差异表达基因进行生物信息学分析，包括 GO 分析、KEGG 分析和 PPI 网络分析，以探索其功能：结果：三种疼痛模型的基因表达存在共性和显著差异。与Sham相比，三种模型中有60个共有差异基因，主要参与氧化磷酸化相关的生物学过程（如mt-Nd1）。与CCI相比，SNI上调的基因与炎症反应有关（如Ifi204、Ifi27），而下调的基因与微管运动有关（如Dnah7b、Hcmn1）；与SNI相比，CFA上调的基因与轴突发育有关（如Oprm1、Gucy1）、Oprm1、Gucy1a2、Syn3），而下调基因与氧化磷酸化有关（如Rpl41、Rpl21）；与CCI相比，CFA上调基因与轴突发育有关（如Zbtb16），而下调基因与氧化磷酸化有关（如Cyp3a13）：结论：三种广泛使用的慢性疼痛模型既有相似之处，也有不同之处。

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引用次数: 0

Direct hybridization and bioinformatics analysis of circulating microRNAs in patients with Alzheimer’s disease under intravenous trehalose treatment

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-03 DOI: 10.1016/j.brainres.2025.149607

Shabnam Radbakhsh , Diana Marisol Abrego-Guandique , Tiziana Bacchetti , Seyed Hamid Aghaee-Bakhtiari , Ali Mahmoudi , Ali Akhonpour Manteghi , Mohammad Javad Bazyari , Erika Cione , Gianna Ferretti , Amirhossein Sahebkar

Trehalose has been proposed as a possible therapeutic option for attenuating the neuropathological changes associated with neurodegeneration, including Alzheimer’s disease (AD). The administration of trehalose in human and murine models was linked to restoring antioxidant status, decreasing lipoperoxidation, and alleviating neuroinflammation. This latter biochemical mechanism was associated with the upregulation of specific brain-enriched microRNAs (miRNA). Herein, using a direct hybridization approach, we evaluate trehalose intravenous treatment in AD patients, conducting a phase two clinical trial (IRCT20130829014521N15) examining the alteration of microRNA profiles before and after the treatment. Twenty patients were recruited and randomly assigned to two groups: the intervention group received 15 g/week of intravenous trehalose. The control group received placebo in the form of normal saline. The period chosen was 12 weeks. Blood samples were obtained at the beginning and end of the study. Circulating microRNAs expression data between the placebo and treatment groups were assessed using microarray analysis. Subsequently, differentially expressed (DE) miRNAs specific to the trehalose-treated group were identified, and their gene targets were determined by bioinformatics-based approaches. The analysis of DE miRNAs pointed out modulation in unique miRNAs between treatment and placebo groups. Specifically, hsa-miR-1268a, −3605-3p, −555, and −6511a-3p were significantly downregulated, while hsa-miR-324-3p and −539-5p showed significant upregulation. Of the 147 overlapped validated genes identified in the bioinformatics analysis, several are related to autophagy, protein aggregation, oxidative stress, and inflammation. KEGG enrichment pathways reveal regulation of actin cytoskeleton, axon guidance, and neurotrophin signaling pathways. The results identify significant modulation in unique miRNAs in AD patients under trehalose. These findings suggest the potential utility of these microRNAs as biomarkers for trehalose pharmacological monitoring in AD.

{"title":"Direct hybridization and bioinformatics analysis of circulating microRNAs in patients with Alzheimer’s disease under intravenous trehalose treatment","authors":"Shabnam Radbakhsh , Diana Marisol Abrego-Guandique , Tiziana Bacchetti , Seyed Hamid Aghaee-Bakhtiari , Ali Mahmoudi , Ali Akhonpour Manteghi , Mohammad Javad Bazyari , Erika Cione , Gianna Ferretti , Amirhossein Sahebkar","doi":"10.1016/j.brainres.2025.149607","DOIUrl":"10.1016/j.brainres.2025.149607","url":null,"abstract":"<div><div>Trehalose has been proposed as a possible therapeutic option for attenuating the neuropathological changes associated with neurodegeneration, including Alzheimer’s disease (AD). The administration of trehalose in human and murine models was linked to restoring antioxidant status, decreasing lipoperoxidation, and alleviating neuroinflammation. This latter biochemical mechanism was associated with the upregulation of specific brain-enriched microRNAs (miRNA). Herein, using a direct hybridization approach, we evaluate trehalose intravenous treatment in AD patients, conducting a phase two clinical trial (IRCT20130829014521N15) examining the alteration of microRNA profiles before and after the treatment. Twenty patients were recruited and randomly assigned to two groups: the intervention group received 15 g/week of intravenous trehalose. The control group received placebo in the form of normal saline. The period chosen was 12 weeks. Blood samples were obtained at the beginning and end of the study. Circulating microRNAs expression data between the placebo and treatment groups were assessed using microarray analysis. Subsequently, differentially expressed (DE) miRNAs specific to the trehalose-treated group were identified, and their gene targets were determined by bioinformatics-based approaches. The analysis of DE miRNAs pointed out modulation in unique miRNAs between treatment and placebo groups. Specifically, hsa-miR-1268a, −3605-3p, −555, and −6511a-3p were significantly downregulated, while hsa-miR-324-3p and −539-5p showed significant upregulation. Of the 147 overlapped validated genes identified in the bioinformatics analysis, several are related to autophagy, protein aggregation, oxidative stress, and inflammation. KEGG enrichment pathways reveal regulation of actin cytoskeleton, axon guidance, and neurotrophin signaling pathways. The results identify significant modulation in unique miRNAs in AD patients under trehalose. These findings suggest the potential utility of these microRNAs as biomarkers for trehalose pharmacological monitoring in AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1857 ","pages":"Article 149607"},"PeriodicalIF":2.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785856","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}

引用次数: 0

Protection of dauricine and daurisoline on PC12 cells damaged by glutamate or Aβ25-35

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-02 DOI: 10.1016/j.brainres.2025.149609

Xiao-Han Ma , Hui Dai , Song-Yao Liu , Xiao-Na Liu , Jing Zhang , Xue-Lian Meng

Glutamate (Glu) excitotoxicity and amyloid-β (Aβ) deposition are significant factors in the occurrence and development of Alzheimer’s disease (AD). Dauricine and daurisoline are two alkaloid components of Menispermum dauricum DC. that have a protective effect on the nervous system. The protection of dauricine and daurisoline on Glu-injured PC12 cells and the protection dauricine on Aβ_25-35-injured PC12 cells were investigated in this study. The results of the study demonstrated that on PC12 cells damaged by Glu (20 mM), dauricine and daurisoline (3 and 10 μM) increased the cell viability, reduced cell apoptosis, and enhanced mitochondrial membrane potential (MMP) levels. Dauricine and daurisoline can also reduce the levels of intracellular ROS and free Ca²⁺, and suppression the expression of CaM, p-CaMKII, and p-Tau in Glu-damaged PC12 cells. In addition, on PC12 cells damaged by Aβ_25-35 (30 μM), dauricine (3 and 10 μM) can also significantly increase the cell viability and MMP levels, inhibit cell apoptosis, reduce intracellular ROS and free Ca²⁺ levels, and down-regulate protein expression of CaM, p-CaMKII, and p-Tau. This study demonstrates for the first time that dauricine and daurisoline may inhibit the excessive phosphorylation of Tau protein and subsequent cell apoptosis by suppressing the Ca²⁺-CaM/CaMKII pathway, thereby protecting PC12 cells damaged Glu or Aβ_25-35 in vitro. Dauricine and daurisoline have the potential to treat AD effectively and have further research value.

谷氨酸（Glu）兴奋毒性和淀粉样蛋白-β（Aβ）沉积是阿尔茨海默病（AD）发生和发展的重要因素。金丝桃碱和金丝桃碱是金丝桃（Menispermum dauricum DC.）的两种生物碱成分，对神经系统具有保护作用。本研究探讨了金丝桃碱和金丝桃碱对 Glu 损伤的 PC12 细胞的保护作用，以及金丝桃碱对 Aβ25-35 损伤的 PC12 细胞的保护作用。研究结果表明，在受到 Glu（20 mM）损伤的 PC12 细胞中，金丝桃碱和金丝桃碱（3 μM 和 10 μM）能提高细胞活力，减少细胞凋亡，提高线粒体膜电位（MMP）水平。去甲乌头碱和去甲乌头碱还能降低细胞内 ROS 和游离 Ca2+ 的水平，抑制 Glu 损伤的 PC12 细胞中 CaM、p-CaMKII 和 p-Tau 的表达。此外，在受到Aβ25-35（30 μM）损伤的PC12细胞中，金丝桃碱（3 μM和10 μM）也能显著提高细胞活力和MMP水平，抑制细胞凋亡，降低细胞内ROS和游离Ca2+水平，下调CaM、p-CaMKII和p-Tau的蛋白表达。本研究首次证明，去甲乌头碱和去甲乌头碱可通过抑制 Ca2+-CaM/CaMKII 通路，抑制 Tau 蛋白的过度磷酸化和随后的细胞凋亡，从而保护体外受损的 Glu 或 Aβ25-35 PC12 细胞。Dauricine和daurisoline具有有效治疗AD的潜力，具有进一步的研究价值。

{"title":"Protection of dauricine and daurisoline on PC12 cells damaged by glutamate or Aβ25-35","authors":"Xiao-Han Ma , Hui Dai , Song-Yao Liu , Xiao-Na Liu , Jing Zhang , Xue-Lian Meng","doi":"10.1016/j.brainres.2025.149609","DOIUrl":"10.1016/j.brainres.2025.149609","url":null,"abstract":"<div><div>Glutamate (Glu) excitotoxicity and amyloid-β (Aβ) deposition are significant factors in the occurrence and development of Alzheimer’s disease (AD). Dauricine and daurisoline are two alkaloid components of <em>Menispermum dauricum</em> DC<em>.</em> that have a protective effect on the nervous system. The protection of dauricine and daurisoline on Glu-injured PC12 cells and the protection dauricine on Aβ<sub>25-35</sub>-injured PC12 cells were investigated in this study. The results of the study demonstrated that on PC12 cells damaged by Glu (20 mM), dauricine and daurisoline (3 and 10 μM) increased the cell viability, reduced cell apoptosis, and enhanced mitochondrial membrane potential (MMP) levels. Dauricine and daurisoline can also reduce the levels of intracellular ROS and free Ca<sup>2+</sup>, and suppression the expression of CaM, p-CaMKII, and p-Tau in Glu-damaged PC12 cells. In addition, on PC12 cells damaged by Aβ<sub>25-35</sub> (30 μM), dauricine (3 and 10 μM) can also significantly increase the cell viability and MMP levels, inhibit cell apoptosis, reduce intracellular ROS and free Ca<sup>2+</sup> levels, and down-regulate protein expression of CaM, p-CaMKII, and p-Tau. This study demonstrates for the first time that dauricine and daurisoline may inhibit the excessive phosphorylation of Tau protein and subsequent cell apoptosis by suppressing the Ca<sup>2+</sup>-CaM/CaMKII pathway, thereby protecting PC12 cells damaged Glu or Aβ<sub>25-35</sub> <em>in vitro</em>. Dauricine and daurisoline have the potential to treat AD effectively and have further research value.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1857 ","pages":"Article 149609"},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776621","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}

引用次数: 0

Researching the causal relationship between immune cells and frontotemporal Dementia: A Mendelian Randomization analysis 研究免疫细胞与额颞叶痴呆症之间的因果关系：孟德尔基因组化分析

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-02 DOI: 10.1016/j.brainres.2025.149608

Yueming Cheng , Xia He , Xialian Huang , Fengle Mao , Fuli Qin , Yanqiu Wang

Background

Frontotemporal dementia (FTD) is a prevalent dementia syndrome with poorly understood immunological underpinnings. Despite the widespread adoption of high-density genotyping technologies like SNPs and CNVs, and advances in genome-wide association studies (GWAS), the immunological mechanisms underlying FTD remain elusive. This study aims to elucidate the causal relationships between immune cell traits and FTD using Mendelian randomization (MR).

Methods

We utilized summary data for FTD (cases = 129, controls = 392,463) from the FinnGen dataset and summary statistics for 731 immune cell traits from the GWAS catalog. These traits included morphological parameters (MP = 32), median fluorescence intensity (MFI = 389), absolute cell counts (AC = 118), and relative cell counts (RC = 192). Our approach encompassed forward MR (immune cell traits as exposure) and reverse MR (FTD as exposure), accompanied by rigorous sensitivity analyses to assess the robustness and heterogeneity of the findings.

Results

FTD did not have a statistically significant impact on immune phenotypes. Notably, we identified 13 immune phenotypes as protective against FTD, including various T cell and B cell markers. Conversely, 8 phenotypes were associated with increased FTD risk, involving markers on myeloid cells and subsets of T and B cells;

Conclusion

This MR study identifies specific immune phenotypes associated with FTD, highlighting potential pathways for future clinical research and therapeutic intervention.

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引用次数: 0

A 40-year analysis of central neuroanatomical and neurochemical circuits mediating homeostatic intake and hedonic intake and preferences in rodents

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-04-01 DOI: 10.1016/j.brainres.2025.149604

Richard J. Bodnar

This perspective review was written in response to the celebration of the 60th anniversary of the journal, Brain Research, and covers the evolving focus of my laboratory’s work over 40 years in the neurobiological substrates of ingestive behavior in rodents. Following our initial work examining the effects of systemic and ventricular administration of general and selective opioid receptor agonists and antagonists on food intake under spontaneous, deprivation, glucoprivic and hedonic conditions, my laboratory in close collaboration with Drs. Gavril Pasternak and Ying-Xian Pan utilized an antisense oligodoxynucleotide knock-down technique affecting MOR-1, DOR-1, KOR-1 and ORL-1 genes as well as against G-protein subunits to study receptor mediation of opioid receptor agonist-induced feeding as well as feeding following regulatory challenges. Our laboratory employed intracerebral microinjection techniques to map limbic nucleus accumbens and ventral tegmental central brain circuits mediating homeostatic and hedonic feeding responses through the use of selective mu, delta₁, delta₂ and kappa opioid receptor subtype agonists in combination with general and selective opioid, dopamineric, glutamatergic and GABAergic antagonists administered into the same site or the reciprocal site, allowing for the identification of a distributed brain network mediating these ingestive effects. Our laboratory in close collaboration with Dr. Anthony Sclafani then focused on the pharmacological, neuroanatomical and learning mechanisms related to the development of sugar- (sucrose, glucose and fructose) and fat- (corn oil) conditioned flavor preferences (CFP) in rats, and on murine genetic variance in food intake, preferences and the process of appetition.

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引用次数: 0