Journal of Neuroscience Research最新文献_第4页

Correction to “Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain” 更正“表没食子儿茶素没食子酸酯和Punicalagin组合减少Aβ聚集并促进成年斑马鱼大脑神经发生”。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-03-11 DOI: 10.1002/jnr.70122

引用次数: 0

Chondroitin Sulfate Proteoglycans in CNS Development and Pathophysiology 硫酸软骨素蛋白聚糖在中枢神经系统发育和病理生理中的作用。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-02-28 DOI: 10.1002/jnr.70115

Seyed Mojtaba Hosseini, Soheila Karimi-Abdolrezaee

{"title":"Chondroitin Sulfate Proteoglycans in CNS Development and Pathophysiology","authors":"Seyed Mojtaba Hosseini, Soheila Karimi-Abdolrezaee","doi":"10.1002/jnr.70115","DOIUrl":"10.1002/jnr.70115","url":null,"abstract":"<p>Chondroitin sulfate proteoglycans (CSPGs) are major components of the matrix in many tissues including the central nervous system (CNS). Interactions between extracellular CSPGs and different cell types are crucial for the development of the CNS as CSPGs are heavily involved in maintaining the pool of progenitors, neurogenesis, neuronal migration and maturation, cortical lamination, synapse formation and stabilization, neuronal plasticity, and memory formation. CSPGs play distinct roles in CNS development and pathology. While physiologic levels of CSPGs have key roles in CNS development, CNS pathologies result in upregulation of CSPGs that pose a barrier to neuroregeneration. Extensive evidence shows that pathologic CSPGs interfere with various regenerative mechanisms including axonal elongation, immunomodulation, synaptogenesis, cellular replacement, and remyelination. At the cellular level, CSPGs' effects are mainly mediated through activation of leukocyte common antigen-related receptor (LAR) and protein tyrosine phosphatase sigma (PTP-σ) receptors. Various approaches have been developed to overcome the inhibitory effects of pathologic CSPGs including enzymatic degradation of CSPGs, blocking CSPG/LAR/PTP-σ axis, and inhibition of CSPGs synthesis. Here, we will discuss the current understanding on the role and mechanisms of CSPGs in CNS development and pathologies and signaling pathways that mediate CSPGs' effects in the CNS. We will also review how CSPGs have been modulated in neurological disorders.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNAseq Analysis of the Cerebellum Reveals Significant Gene Dysregulation That May Explain Chronic Disease Progression in Mild Traumatic Brain Injury 小脑的RNAseq分析揭示了可能解释轻度创伤性脑损伤慢性疾病进展的显著基因失调。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-02-18 DOI: 10.1002/jnr.70105

Katy M. Li, Anna Balzer, Thomas M. Doering, Matthew I. Hiskens, Ryan du Preez, Andrew S. Fenning

{"title":"RNAseq Analysis of the Cerebellum Reveals Significant Gene Dysregulation That May Explain Chronic Disease Progression in Mild Traumatic Brain Injury","authors":"Katy M. Li, Anna Balzer, Thomas M. Doering, Matthew I. Hiskens, Ryan du Preez, Andrew S. Fenning","doi":"10.1002/jnr.70105","DOIUrl":"10.1002/jnr.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Mild traumatic brain injury (mTBI) is a major public health concern worldwide and contributes to chronic, persistent neurodegenerative diseases; however, the mechanisms are not fully understood. Most studies have examined cerebral cortex, hippocampus, and thalamus brain tissue, but the impact on the cerebellum following repetitive mTBI (rmTBI) leading to secondary injury cascades and long-term pathophysiology is largely unexplored. This study investigated changes in gene expression in cerebellum tissue from an established murine model of rmTBI. The cerebellum tissue from 15 male C57BL/6J mice was analyzed using RNA sequencing technology for animals sacrificed 48 h (acute) and 90 days (chronic) following a repetitive mild impact schedule. Differentially expressed gene (DEG) analysis showed no dysregulated genes above log2 fold change at 48 h, but 360 DEGs at 90 days. At 90 days, multiple Gene Ontologies were different to controls, including disruption to mitochondria, proteosomes, ribosomes, and a reduction in vital cellular energy processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis in the chronic injury group revealed that dysregulated genes were characteristic of multiple neurological diseases, including <i>Parkinson's</i> and <i>Huntington's disease</i> genetic signatures. This data demonstrates that the cerebellum and other brain regions disparate from the site of impact are more than just a bystander in chronic neurodegenerative pathologies and provides a vital link to the development of neurological disorders like Parkinson's disease from rmTBI trauma.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220118","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

Purkinje Cells as Gatekeepers of Seizure Susceptibility: Insights From Optogenetics 浦肯野细胞作为癫痫易感性的看门人：来自光遗传学的见解。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-02-11 DOI: 10.1002/jnr.70118

Sara Bernardi, Federica Gemignani, Filippo M. Santorelli, Maria Marchese

{"title":"Purkinje Cells as Gatekeepers of Seizure Susceptibility: Insights From Optogenetics","authors":"Sara Bernardi, Federica Gemignani, Filippo M. Santorelli, Maria Marchese","doi":"10.1002/jnr.70118","DOIUrl":"10.1002/jnr.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Purkinje cells (PCs), the principal output neurons of the cerebellar cortex, are classically implicated in motor coordination via inhibitory projections to the deep cerebellar nuclei (DCN). Emerging evidence suggests their influence extends to seizure susceptibility, yet the underlying mechanisms remain unclear. Here, we investigated the functional role of PCs in locomotion and seizure-like activity in zebrafish larvae. Using the UAS/Gal4 system, we selectively expressed light-sensitive ion channels in PCs: Channelrhodopsin-2 (ChR2) to activate, and Anion ChannelRhodopsin-2 (ACR2) to inhibit neuronal activity. Behavioral assays at 5 days post-fertilization assessed locomotor output, while local field potential recordings monitored seizure-like events under baseline conditions and following administration of a proconvulsant agent. Optogenetic activation of PCs transiently increased locomotion and significantly reduced the duration and power of seizure-like events under hyperexcitable conditions, without affecting baseline activity. Conversely, inhibition of PCs was sufficient to induce seizure-like activity even in the absence of convulsant stimuli. These results reveal a dual role for PCs: they suppress pathological hyperexcitability during proconvulsant states, yet their inhibition can trigger seizures. This work highlights the cerebellum as a critical regulator of excitation-inhibition balance, linking motor control and seizure susceptibility, and suggests that cerebellar dysfunction may contribute to both motor and epileptic phenotypes observed in neurodegenerative disorders.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165476","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

Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain 表没食子儿茶素没食子酸酯和甘油三酯联合减少Aβ聚集并促进成年斑马鱼大脑神经发生。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-02-11 DOI: 10.1002/jnr.70119

Dilek Nazli, Dogac Ipekgil, Yusuf Kaan Poyraz, Kubilay Can, Ilke Okmen, Ebru Turhanlar-Sahin, Belgin Sert Serdar, Semra Kocturk, Gunes Ozhan

{"title":"Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain","authors":"Dilek Nazli, Dogac Ipekgil, Yusuf Kaan Poyraz, Kubilay Can, Ilke Okmen, Ebru Turhanlar-Sahin, Belgin Sert Serdar, Semra Kocturk, Gunes Ozhan","doi":"10.1002/jnr.70119","DOIUrl":"10.1002/jnr.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165485","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

Sex Differences in Markers of Neuronal Adaptation in the Medullary Dorsal Horn During the Development of Orofacial Neuropathic Pain 颅面神经性疼痛发生过程中髓背角神经元适应标记物的性别差异。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-02-02 DOI: 10.1002/jnr.70117

Hyunsol Lim, James W. M. Kang, Luke A. Henderson, Kevin A. Keay

{"title":"Sex Differences in Markers of Neuronal Adaptation in the Medullary Dorsal Horn During the Development of Orofacial Neuropathic Pain","authors":"Hyunsol Lim, James W. M. Kang, Luke A. Henderson, Kevin A. Keay","doi":"10.1002/jnr.70117","DOIUrl":"10.1002/jnr.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic trigeminal neuropathic pain is caused by a lesion, damage, or trauma to the trigeminal sensory system. The pain affects female individuals with higher incidence and greater severity compared with males. Despite a strong sex bias in this clinical condition, the majority of preclinical experimental studies of trigeminal neuropathic pain have been conducted in males. This study investigated sex differences in the number of ΔFosB and FosB immunoreactive cells, as markers of neuronal adaptation following infraorbital nerve chronic constriction injury (ION-CCI). Sex differences in ΔFosB and FosB expression were identified in infra-orbital recipient regions of laminae I-II of the medullary dorsal horn during the post-injury period. Three phases of altered expression were identified following ION-CCI: (1) an early phase 2 days after injury, (2) a transitional phase (7–14 days), and (3) a late phase (28+ days). Nerve-injured female rats had consistently lower levels of ΔFosB immunoreactive cells when compared with males and showed increased FosB expression during the early phase. In contrast, in males, the number of ΔFosB immunoreactive cells decreased significantly from the early phase to the transitional phase post-injury. However, by the late phase, ΔFosB expression in the superficial laminae of the medullary dorsal horn was significantly higher than in females. These data suggest that cellular adaptation in neurons in laminae I-II of the medullary dorsal horn in males is much greater than that in females, revealing one location at which the sex differences seen in the incidence and severity of trigeminal neuropathic pain might be mediated.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105864","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

Bone Marrow Mesenchymal Stem Cells Improve Cognitive Impairment Induced by Neuropathic Pain Through Blood CXCL12/CXCR4 Axis in Male Mice 骨髓间充质干细胞通过血液CXCL12/CXCR4轴改善雄性小鼠神经性疼痛诱导的认知障碍

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-01-28 DOI: 10.1002/jnr.70111

Kai Sun, Le Qi, Hao Zhang, Liwei Wang, Ting Zhang

{"title":"Bone Marrow Mesenchymal Stem Cells Improve Cognitive Impairment Induced by Neuropathic Pain Through Blood CXCL12/CXCR4 Axis in Male Mice","authors":"Kai Sun, Le Qi, Hao Zhang, Liwei Wang, Ting Zhang","doi":"10.1002/jnr.70111","DOIUrl":"10.1002/jnr.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent evidence has shown that bone marrow mesenchymal stem cells (BMSCs) have multiple biological applications and play an important role in improving cognitive dysfunction. However, it is still unclear whether BMSCs play a role in cognitive impairment induced by chronic pain. This study aimed to evaluate the therapeutic effect of BMSCs on neuropathic pain-induced cognitive dysfunction and explore its potential mechanisms. A mouse chronic constriction injury (CCI) model was established, and the new object recognition task and fear conditioning were used to detect cognitive function; the expression of CXCL12/CXCR4 in blood and hippocampus was detected. After intravenous injection of BMSCs, changes in cognitive function and expression of the CXCL12/CXCR4 pathway, dentate gyrus neurogenesis, and excitability of hippocampal neurons were detected. In addition, induction of cognitive impairment in normal mice by CXCL12 recombinant protein was used to clarify whether the CXCL12/CXCR4 pathway mediates the cognitive function improvement effect of BMSCs. Our results found CCI mice showed significant cognitive impairment 21 days after surgery, with significantly increased expression of CXCL12/CXCR4 in blood and hippocampus. Intravenous injection of BMSCs significantly improved cognitive function, inhibited expression of CXCL12/CXCR4 in blood and hippocampus, promoted neurogenesis in dentate gyrus of CCI mice, and increased expression of BDNF and c-Fos in the hippocampus. In addition, BMSCs alleviate cognitive impairment induced by intravenous injection of CXCL12 recombinant protein in mice. In summary, BMSCs improve chronic neuropathic pain-induced cognitive dysfunction through peripheral blood CXCL12/CXCR4, and BMSCs may develop into therapeutic targets for chronic pain induced cognitive impairment.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064289","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

The Identification of Mitochondrial-Related Biomarkers of Ruptured Intracranial Aneurysms Based on Bioinformatics Analysis and Machine Learning 基于生物信息学分析和机器学习的颅内动脉瘤破裂线粒体相关生物标志物鉴定。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-01-26 DOI: 10.1002/jnr.70114

Yao Li, Dezhang Huang, Zeyu Wu, Tao Liu, Peng Sun

{"title":"The Identification of Mitochondrial-Related Biomarkers of Ruptured Intracranial Aneurysms Based on Bioinformatics Analysis and Machine Learning","authors":"Yao Li, Dezhang Huang, Zeyu Wu, Tao Liu, Peng Sun","doi":"10.1002/jnr.70114","DOIUrl":"10.1002/jnr.70114","url":null,"abstract":"<div>\u0000 \u0000 <p>Intracranial aneurysms (IAs) are pathological dilatations of cerebral blood vessels, and their rupture can lead to severe mortality and disability. Therefore, identifying those at risk of rupture is of considerable clinical significance. We screened 3740 differentially expressed genes (DEGs) in ruptured IA (RIA) versus unruptured IA (UIA) from the GSE13353 dataset. Weighted gene co-expression network analysis (WGCNA) was used to identify RIA-related module genes. After the intersection of DEGs and module genes with mitochondria-related genes (MRGs), MTX1, BCL2A1, BID, UCP2, ME2, VAV1, CYBA, and CYBB were identified as mitochondria-associated signatures of RIA. MTX1 was identified as the key diagnostic biomarker using three machine learning methods. While the diagnostic potential of this eight-gene signature was supported by an independent dataset (GSE122897), experimental validation in clinical and animal models confirmed significant dysregulation of ME2, UCP2, BCL2A1, and CYBA in RIA. Notably, MTX1 showed a consistent but non-significant trend of downregulation in these experimental assays. Immune infiltration analysis revealed a pro-inflammatory and stromal-enriched microenvironment in RIA, characterized by significantly elevated abundances of fibroblasts, smooth muscle cells, and macrophages, and showing distinct correlation patterns between key mitochondrial genes and specific immune and stromal cell populations. The construction of transcription factors and endogenous RNA networks was used to identify the underlying molecular mechanisms. Finally, potential therapeutic drugs such as rosiglitazone were identified by drug prediction, and the molecular docking of ME2 with cryptotanshinone suggested a new therapeutic approach. This study may provide a new strategy for the diagnosis and treatment of RIA targeting mitochondria.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052543","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

Pharmacological Inhibition of EZH2 by GSK-343 Attenuates Neuroinflammation in a Mouse Model of Spinal Cord Injury GSK-343对EZH2的药理抑制减轻脊髓损伤小鼠模型的神经炎症

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-01-20 DOI: 10.1002/jnr.70104

Yinhui Kang, Deborah Mannino, Valentina Bova, Alberto Repici, Bulzomì Maria, Ahmed Hasan, Antonio Catalfamo, Jia Yang, Marika Lanza, Alessia Filippone

{"title":"Pharmacological Inhibition of EZH2 by GSK-343 Attenuates Neuroinflammation in a Mouse Model of Spinal Cord Injury","authors":"Yinhui Kang, Deborah Mannino, Valentina Bova, Alberto Repici, Bulzomì Maria, Ahmed Hasan, Antonio Catalfamo, Jia Yang, Marika Lanza, Alessia Filippone","doi":"10.1002/jnr.70104","DOIUrl":"10.1002/jnr.70104","url":null,"abstract":"<p>Spinal cord injury (SCI) is a devastating condition with limited therapeutic options and a strong neuroinflammatory component that exacerbates tissue damage and impairs functional recovery. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and core component of the Polycomb Repressive Complex 2 (PRC2), has emerged as a key regulator of epigenetic modifications involved in neuroinflammation. In this study, we investigated the potential neuroprotective effects of GSK-343, a selective EZH2 inhibitor, in a murine model of SCI induced by extradural compression. Female adult CD1 mice received intraperitoneal injections of GSK-343 (1, 5, or 10 mg/kg) at 1- and 6-h post-injury. After 24 h, spinal cord tissues were collected and analyzed. GSK-343 treatment significantly reduced histological damage, neuronal demyelination, and the expression of pro-inflammatory markers, likely through modulation of the TRAF6/NF-κB signaling pathway. Moreover, EZH2 inhibition attenuated innate immune responses, as evidenced by the reduction in mast cell infiltration, microglial activation, and MCP-1 levels. These findings support the therapeutic potential of EZH2 inhibition as a novel epigenetic strategy to counteract neuroinflammation and promote early neuroprotection following SCI.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Functional Epididymal Amyloid Cystatin-Related Epididymal Spermatogenic (CRES) is a Component of the Mammalian Brain Extracellular Matrix 功能性附睾淀粉样半胱抑素相关附睾生精（CRES）是哺乳动物脑细胞外基质的一个组成部分。

IF 3.4 3区医学

Journal of Neuroscience Research Pub Date : 2026-01-20 DOI: 10.1002/jnr.70113

Alejandra Gomez, Uyen T. Tran, Petar N. Grozdanov, Gail A. Cornwall

{"title":"The Functional Epididymal Amyloid Cystatin-Related Epididymal Spermatogenic (CRES) is a Component of the Mammalian Brain Extracellular Matrix","authors":"Alejandra Gomez, Uyen T. Tran, Petar N. Grozdanov, Gail A. Cornwall","doi":"10.1002/jnr.70113","DOIUrl":"10.1002/jnr.70113","url":null,"abstract":"<p>CRES is the defining member of a reproductive subgroup of family 2 cystatins of cysteine protease inhibitors. We previously showed that CRES and other subgroup members are part of a highly plastic amyloid-containing extracellular matrix (ECM) with host defense functions in the mouse epididymal lumen. Based on parallels between the epididymis and the brain, we hypothesized that CRES and CRES amyloids might also function within the brain including the ECM. Here we show that CRES is produced by hippocampal neurons and astrocytes in the male and female mouse and human brain. Further, approximately 50% of hippocampal astrocytes from aged mice, like the aged human donor samples, had significantly reduced levels of CRES compared to younger mice, suggesting an age-related decline in CRES could contribute to altered brain function. Immunofluorescence experiments showed CRES colocalized with the ECM markers phosphacan and <i>wisteria floribunda</i> agglutinin indicating that CRES is part of the ECM. CRES monomer and high molecular weight SDS-resistant forms were found in insoluble fractions of the hippocampus, cortex, cerebellum, and midbrain and bound to the protein aggregation disease (PAD) ligand, which preferentially binds amyloids but not protein monomers, suggesting a population of CRES normally exists in the brain as an amyloid structure. Collectively, our studies demonstrate that CRES/CRES amyloid is present in the mammalian brain and may contribute to ECM structure and function.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0