Journal of Molecular Neuroscience最新文献_第6页

Calycosin promotes axon growth by inhibiting PTPRS and alleviates spinal cord injury 萼萼素能通过抑制 PTPRS 促进轴突生长，缓解脊髓损伤。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-06-21 DOI: 10.1007/s12031-024-02235-1

Tianqi Jiang, Aitao Wang, Guangyu Wen, Hao Qi, Yuntao Gu, Wenhai Tang, Chunzhao Xu, Shanwu Ren, Shunli Zhang, Shengxing Liu, Yongxiong He

{"title":"Calycosin promotes axon growth by inhibiting PTPRS and alleviates spinal cord injury","authors":"Tianqi Jiang, Aitao Wang, Guangyu Wen, Hao Qi, Yuntao Gu, Wenhai Tang, Chunzhao Xu, Shanwu Ren, Shunli Zhang, Shengxing Liu, Yongxiong He","doi":"10.1007/s12031-024-02235-1","DOIUrl":"10.1007/s12031-024-02235-1","url":null,"abstract":"<div><p>Our former studies have identified the alleviating effect of Calycosin (CA) on spinal cord injury (SCI). In this study, our purpose is to explore the influence of CA on SCI from the perspective of promoting axon growth. The SCI animal model was constructed by spinal cord compression, wherein rat primary cortex neuronal isolation was performed, and the axonal growth restriction cell model was established via chondroitin sulfate proteoglycan (CSPG) treatment. The expressions of axon regeneration markers were measured via immunofluorescent staining and western blot, and the direct target of CA was examined using silver staining. Finally, the expression of the protein tyrosine phosphatase receptor type S (PTPRS) was assessed using western blot. CA treatment increased neuronal process outgrowth and the expressions of axon regeneration markers, such as neurofilament H (NF-H), vesicular glutamate transporter 1 (vGlut1), and synaptophysin (Syn) in both SCI model rats and CSPG-treated primary cortical neurons, and PTPRS levels were elevated after SCI induction. In addition, PTPRS was the direct target of CA, and according to in vivo findings, exposure to CA reduced the PTPRS content. Furthermore, PTPRS overexpression inhibited CA’s enhancement of axon regeneration marker content and neuronal axon lengths. CA improves SCI by increasing axon development through regulating PTPRS expression.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431018","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

BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF BCI通过恢复pERK-BDNF改善酒精引起的认知和情感障碍

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-06-18 DOI: 10.1007/s12031-024-02237-z

Sasa Wang, Xinlei Zhang, Yuru Zhao, Haoxuan Lv, Pengyu Li, Zhihao Zhang, Xiaomeng Qiao

{"title":"BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF","authors":"Sasa Wang, Xinlei Zhang, Yuru Zhao, Haoxuan Lv, Pengyu Li, Zhihao Zhang, Xiaomeng Qiao","doi":"10.1007/s12031-024-02237-z","DOIUrl":"10.1007/s12031-024-02237-z","url":null,"abstract":"<div><p>Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417145","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

Correction to: Expanding the Phenotypic Spectrum of APMR4 Syndrome Caused by a Novel Variant in LSS Gene 更正：扩展由 LSS 基因新型变异引起的 APMR4 综合征的表型谱。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-06-01 DOI: 10.1007/s12031-024-02233-3

Nesma M. Elaraby, Hoda A. Ahmed, Neveen A. Ashaat, Sameh Tawfik, Mahmoud K. H. Ahmed, Nehal F. Hassib, Engy A. Ashaat

引用次数: 0

Evaluating CXCL12 for Effects on Reactive Gene Expression in Primary Astrocytes 评估 CXCL12 对原代星形胶质细胞中活性基因表达的影响

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-28 DOI: 10.1007/s12031-024-02231-5

Konstanze Zieger, Carolina Cao, Jürgen Engele

{"title":"Evaluating CXCL12 for Effects on Reactive Gene Expression in Primary Astrocytes","authors":"Konstanze Zieger, Carolina Cao, Jürgen Engele","doi":"10.1007/s12031-024-02231-5","DOIUrl":"10.1007/s12031-024-02231-5","url":null,"abstract":"<div><p>Upon injury to the CNS, astrocytes undergo morphological and functional changes commonly referred to as astrocyte reactivity. Notably, these reactive processes include altered expression of factors that control immune processes and neuronal survival, as well as increased expression of the CXCL12 receptor, CXCR7/ACKR3. We now asked whether these events are related in that the astrocytic CXCL12 system modulates immune responses and/or neuronal survival. Short-term exposure of astrocytes cultured from the postnatal rat cortex to CXCL12 prominently increased the expression of serpine1/PAI1 on the mRNA level, but showed either no or only minor effects on the expression of additional reactive genes, selected from previous array studies. CXCL12-induced increases in PAI1 protein levels were only detectable in the additional presence of chemokines/cytokines, suggesting that translation of serpine1 mRNA depends on the cooperation of various factors. As expected, expression of most of the selected genes increased after acute or chronic activation of astrocytes with either LPS or a combination of IL-1β and TNFα. CXCL12 partially attenuated expression of some of the LPS and IL-1β/TNFα-induced genes under acute conditions, in particular those encoding CXCL9, CXCL10, CXCL11, and CCL5. Taken together, these findings argue for the involvement of the astrocyte CXCL12 system in the control of the immune response of the injured CNS, where it may control distinct steps.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157363","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

Discovery of Potential Drug Targeting Key Genes in Alzheimer’s Disease: Insights from Transcriptome Analysis and Molecular Docking 发现针对阿尔茨海默病关键基因的潜在药物：转录组分析和分子对接的启示。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-27 DOI: 10.1007/s12031-024-02208-4

Hanjie Liu, Hui Yang, Maochun You, Siyu Zhang, Sihan Huang, Xin Tan, Qi Liu, Cen Jiang, Lushuang Xie

{"title":"Discovery of Potential Drug Targeting Key Genes in Alzheimer’s Disease: Insights from Transcriptome Analysis and Molecular Docking","authors":"Hanjie Liu, Hui Yang, Maochun You, Siyu Zhang, Sihan Huang, Xin Tan, Qi Liu, Cen Jiang, Lushuang Xie","doi":"10.1007/s12031-024-02208-4","DOIUrl":"10.1007/s12031-024-02208-4","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder that presents a significant global health challenge. To explore drugs targeting key genes in AD, R software was used to analyze the data of single nuclei transcriptome from human cerebral frontal cortex in AD, and the differentially expressed genes (DEGs) were screened. Then the gene ontology (GO) analysis, Kyoto gene and genome encyclopedia (KEGG) pathway enrichment and protein-protein interaction (PPI) network were analyzed. The hub genes were calculated by Cytoscape software. Molecular docking and molecular dynamics simulation were used to evaluate and visualize the binding between candidate drugs and key genes. A total of 564 DEGs were screened, and the hub genes were ISG15, STAT1, MX1, IFIT3, IFIT2, RSAD2, IFIT1, IFI44, IFI44L and DDX58. Enrichment terms mainly included response to virus, IFN-γ signaling pathway and virus infection. Diclofenac had good binding effect with IFI44 and IFI44L. Potential drugs may act on key gene targets and then regulate biological pathways such as virus response and IFN-γ-mediated signal pathway, so as to achieve anti-virus, improve immune balance and reduce inflammatory response, and thus play a role in anti-AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157362","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

Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer’s Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status 阿尔茨海默病脂质代谢基因转录组分析：突显病理结果和分区免疫状态。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-22 DOI: 10.1007/s12031-024-02225-3

Yue Sun, Mengni Jiang, Xiang Long, Yongzhen Miao, Huanhuan Du, Ting Zhang, Xuejun Ma, Yue Zhang, Hongrui Meng

{"title":"Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer’s Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status","authors":"Yue Sun, Mengni Jiang, Xiang Long, Yongzhen Miao, Huanhuan Du, Ting Zhang, Xuejun Ma, Yue Zhang, Hongrui Meng","doi":"10.1007/s12031-024-02225-3","DOIUrl":"10.1007/s12031-024-02225-3","url":null,"abstract":"<div><p>The dysregulation of lipid metabolism has been strongly associated with Alzheimer’s disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074419","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

Exploring the Biological Overlapping Between Brain Calcifications and Tumorgenesis 探索脑钙化与肿瘤发生之间的生物学重叠。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-17 DOI: 10.1007/s12031-024-02230-6

Enrico Souza de Godoy, João Ricardo Mendes de Oliveira

引用次数: 0

Reversibility of Endoplasmic Reticulum Stress Markers During Long-Term Glucose Starvation in Astrocytes 星形胶质细胞在长期葡萄糖饥饿过程中内质网应激标记物的可逆性

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-16 DOI: 10.1007/s12031-024-02223-5

Clara Voelz, Lena E. M. Schaack, Vanessa Kogel, Cordian Beyer, Jochen Seitz, Stefanie Trinh

{"title":"Reversibility of Endoplasmic Reticulum Stress Markers During Long-Term Glucose Starvation in Astrocytes","authors":"Clara Voelz, Lena E. M. Schaack, Vanessa Kogel, Cordian Beyer, Jochen Seitz, Stefanie Trinh","doi":"10.1007/s12031-024-02223-5","DOIUrl":"10.1007/s12031-024-02223-5","url":null,"abstract":"<div><p>Previous studies have demonstrated a brain volume decrease linked to long-term starvation in patients with anorexia nervosa (AN). Food intake is critically diminished in this disorder, leading to one of the highest mortality rates within the psychiatric disease spectrum. As reported in animal models, astrocytes seem to be the most affected cell type in AN. In a recently established primary cell culture model, an elevated unfolded protein response (UPR) was observed in long-term glucose semi-starved astrocytes. A well-functioning protein machinery is essential for every cell, and prolonged UPR will lead to cell death. As a nucleic acid stress-sensing pathway with the activator located in the endoplasmic reticulum, the regulation of the cGAS-STING pathway (cyclic GMP-AMP synthase/stimulator of interferon genes) was additionally investigated in the starvation context. In the current study, a glucose semi-starvation protocol of 15 days, during which cells were supplied with 2 mM glucose in the medium, was prolonged with an additional 6-day long recovery period. Our findings showed that increased UPR mRNA expression was reversible after re-establishing the standard glucose concentration of 25 mM. Furthermore, we were able to verify the presence of cGAS and STING in astrocytes with a characteristic presence of cGAS in the astrocyte nucleus during starvation. A correlation between STING and the glial fibrillary acidic protein (GFAP) could be established, hinting at a conditional presence of STING with a specific astrocyte phenotype.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy 胶质母细胞瘤中的谷氨酰胺代谢异质性揭示了一种创新的联合疗法策略。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-10 DOI: 10.1007/s12031-024-02201-x

Huangde Fu, Shengtian Wu, Hechun Shen, Kai Luo, Zhongxiang Huang, Nankun Lu, Yaolin Li, Qian Lan, Yishun Xian

{"title":"Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy","authors":"Huangde Fu, Shengtian Wu, Hechun Shen, Kai Luo, Zhongxiang Huang, Nankun Lu, Yaolin Li, Qian Lan, Yishun Xian","doi":"10.1007/s12031-024-02201-x","DOIUrl":"10.1007/s12031-024-02201-x","url":null,"abstract":"<div><p>Treatment of glioblastoma multiforme (GBM) remains challenging. Unraveling the orchestration of glutamine metabolism may provide a novel viewpoint on GBM therapy. The study presented a full and comprehensive comprehending of the glutamine metabolism atlas and heterogeneity in GBM for facilitating the development of a more effective therapeutic choice. Transcriptome data from large GBM cohorts were integrated in this study. A glutamine metabolism-based classification was established through consensus clustering approach, and a classifier by LASSO analysis was defined for differentiating the classification. Prognosis, signaling pathway activity, tumor microenvironment, and responses to immune checkpoint blockade (ICB) and small molecular drugs were characterized in each cluster. A combinational therapy of glutaminase inhibitor CB839 with dihydroartemisinin (DHA) was proposed, and the influence on glutamine metabolism, apoptosis, reactive oxygen species (ROS), and migration was measured in U251 and U373 cells. We discovered that GBM presented heterogeneous glutamine metabolism–based clusters, with unique survival outcomes, activity of signaling pathways, tumor microenvironment, and responses to ICB and small molecular compounds. In addition, the classifier could accurately differentiate the two clusters. Strikingly, the combinational therapy of CB839 with DHA synergistically attenuated glutamine metabolism, triggered apoptosis and ROS accumulation, and impaired migrative capacity in GBM cells, demonstrating the excellent preclinical efficacy. Altogether, our findings unveil the glutamine metabolism heterogeneity in GBM and propose an innovative combination therapy of CB839 with DHA for this malignant disease.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896660","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

Biomarkers of Alzheimer’s Disease Associated with Programmed Cell Death Reveal Four Repurposed Drugs 与程序性细胞死亡相关的阿尔茨海默氏症生物标志物揭示了四种再利用药物。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-05-03 DOI: 10.1007/s12031-024-02228-0

Elif Kubat Oktem

{"title":"Biomarkers of Alzheimer’s Disease Associated with Programmed Cell Death Reveal Four Repurposed Drugs","authors":"Elif Kubat Oktem","doi":"10.1007/s12031-024-02228-0","DOIUrl":"10.1007/s12031-024-02228-0","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia. Programmed cell death (PCD) is mainly characterized by unique morphological features and energy-dependent biochemical processes. The predominant pathway leading to cell death in AD has not been thoroughly analyzed, although there is evidence of neuron loss in AD and numerous pathways of PCD have been associated with this process. A better understanding of the systems biology underlying the relationship between AD and PCD could lead to the development of new therapeutic approaches. To this end, publicly available transcriptome data were examined using bioinformatic methods such as differential gene expression and weighted gene coexpression network analysis (WGCNA) to find PCD-related AD biomarkers. The diagnostic significance of these biomarkers was evaluated using a logistic regression-based predictive model. Using these biomarkers, a multifactorial regulatory network was developed. Last, a drug repositioning study was conducted to propose new drugs for the treatment of AD targeting PCD. The development of 3PM (predictive, preventive, and personalized) drugs for the treatment of AD would be enabled by additional research on the effects of these drugs on this disease.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855121","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