Translational Neuroscience最新文献

{"title":"Trehalose improves the movement ability of Aβ_arc<i>Drosophila</i> by restoring the damaged mitochondria.","authors":"Liangxian Li, Zhiheng Huang, Mingli Wu, Xia Li, Bo Xiao, Dong Yao, Biwen Mo","doi":"10.1515/tnsci-2022-0338","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0338","url":null,"abstract":"<p><strong>Background: </strong>The deposition of Aβ₄₂ has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aβ₄₂ toxicity has been progressed slowly.</p><p><strong>Objective: </strong>Our aim was to introduce the effect and related mechanism of trehalose on an Aβ_arc (arctic mutant Aβ₄₂) <i>Drosophila</i> AD model.</p><p><strong>Methods: </strong>The human Aβ_arc was expressed in <i>Drosophila</i> to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aβ_arc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function.</p><p><strong>Results: </strong>Trehalose strongly improved the movement ability of Aβ_arc <i>Drosophila</i> in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aβ_arc and lactate both in the brain and thorax of Aβ_arc <i>Drosophila</i>. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aβ_arc <i>Drosophila</i>.</p><p><strong>Conclusion: </strong>Trehalose improves movement ability at least partly by reducing the Aβ_arc level and restoring the mitochondrial structure and function in Aβ_arc <i>Drosophila</i>.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220338"},"PeriodicalIF":2.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868193","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}

{"title":"Association between <i>FOXP3</i> polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.","authors":"Jing Liu, Gaoning Wang, Jiahe Yang, Yulin Wang, Ruoyi Guo, Bin Li","doi":"10.1515/tnsci-2022-0337","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0337","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Forkhead box P3 (&lt;i&gt;FOXP3&lt;/i&gt;) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between &lt;i&gt;FOXP3&lt;/i&gt; polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;We genotyped single nucleotide polymorphisms at loci of the &lt;i&gt;FOXP3&lt;/i&gt; gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of &lt;i&gt;FOXP3&lt;/i&gt; in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, &lt;i&gt;p&lt;/i&gt; = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, &lt;i&gt;p&lt;/i&gt; = 0.038). The proportions of the three genotypes of rs2232365 (&lt;i&gt;p&lt;/i&gt; = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS &lt; 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of &lt;i&gt;FOXP3&lt;/i&gt; was markedly greater in the NMOSD group than in the control group (&lt;i&gt;p&lt;/i&gt; = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (&lt;i&gt;p&lt;/i&gt; = 0.004 and 0.007, respectively).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;&lt;i&gt;FOXP3&lt;/i&gt; polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of &lt;i&gt;FOXP3&lt;/i&gt; rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. &lt;i&gt;FOXP3&lt;/i&gt; mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decr","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220337"},"PeriodicalIF":2.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874875","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}

{"title":"Comparative analysis of CRASH and IMPACT in predicting the outcome of 340 patients with traumatic brain injury.","authors":"Tingting An, Zibei Dong, Xiangyang Li, Yifan Ma, Jie Jin, Liqing Li, Lanjuan Xu","doi":"10.1515/tnsci-2022-0327","DOIUrl":"10.1515/tnsci-2022-0327","url":null,"abstract":"<p><strong>Background: </strong>Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population.</p><p><strong>Methods: </strong>We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance.</p><p><strong>Results: </strong>Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively.</p><p><strong>Conclusion: </strong>Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220327"},"PeriodicalIF":2.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289086","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}

{"title":"Early exercise intervention promotes myelin repair in the brains of ischemic rats by inhibiting the MEK/ERK pathway.","authors":"Junyi Wang, Xinyu Ding, Chen Li, Chuan Huang, Changkai Ke, Chunlei Xu, Chunxiao Wan","doi":"10.1515/tnsci-2022-0335","DOIUrl":"10.1515/tnsci-2022-0335","url":null,"abstract":"<p><p>Our previous studies have shown that early exercise intervention after stroke increases neural activity and synaptic plasticity and promotes the recovery of nerve fiber bundle integrity in the brain. However, the effect of exercise on the repair of myelin in the brain and the related mechanism are still unclear. In this study, we randomly divided the rats into three groups. Before and after 28 days of intervention, body weight, nerve function, the infarct size, white matter fiber bundle integrity, and nerve myelin structure and function were observed by measuring body weight, analysis of modified neurological severity score, CatWalk gait analysis, MRI, luxol fast blue staining, immunofluorescence, and transmission electron microscopy. Changes in the expression of proteins in the MEK/ERK pathway were assessed. The results showed that early exercise intervention resulted in neurological recovery, decreased the infarct volume and increased nerve fiber integrity, the myelin coverage area, myelin basic protein (MBP) fluorescence intensity expression, and myelin thickness. Furthermore, the expression level of MBP was significantly increased after early exercise intervention, while the expression levels of p-MEK1/2 and p-ERK1/2 were significantly reduced. In the cell study, MBP expression levels were significantly higher in the oxygen and glucose deprivation and administration group.In summary, early exercise intervention after stroke can promote myelin repair by inhibiting the MEK/ERK signaling pathway.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220335"},"PeriodicalIF":1.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178684","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}

{"title":"Silibinin suppresses glioblastoma cell growth, invasion, stemness, and glutamine metabolism by YY1/SLC1A5 pathway.","authors":"Ming Liu, Xipeng Liu, Jianxin Qiao, Bing Cao","doi":"10.1515/tnsci-2022-0333","DOIUrl":"10.1515/tnsci-2022-0333","url":null,"abstract":"<p><strong>Background: </strong>Silibinin has been found to inhibit glioblastoma (GBM) progression. However, the underlying molecular mechanism by which Silibinin regulates GBM process remains unclear.</p><p><strong>Methods: </strong>GBM cell proliferation, apoptosis, invasion, and stemness are assessed by cell counting kit-8 assay, EdU assay, flow cytometry, transwell assay, and sphere formation assay. Western blot is used to measure the protein expression levels of apoptosis-related markers, solute carrier family 1 member 5 (SLC1A5), and Yin Yang-1 (YY1). Glutamine consumption, glutamate production, and α-ketoglutarate production are detected to evaluate glutamine metabolism in cells. Also, SLC1A5 and YY1 mRNA levels are examined using quantitative real-time PCR. Chromatin immunoprecipitation assay and dual-luciferase reporter assay are used to detect the interaction between YY1 and SLC1A5. Mice xenograft models are constructed to explore Silibinin roles <i>in vivo</i>.</p><p><strong>Results: </strong>Silibinin inhibits GBM cell proliferation, invasion, stemness, and glutamine metabolism, while promotes apoptosis. SLC1A5 is upregulated in GBM and its expression is decreased by Silibinin. SLC1A5 overexpression abolishes the anti-tumor effect of Silibinin in GBM cells. Transcription factor YY1 binds to SLC1A5 promoter region to induce SLC1A5 expression, and the inhibition effect of YY1 knockdown on GBM cell growth, invasion, stemness, and glutamine metabolism can be reversed by SLC1A5 overexpression. In addition, Silibinin reduces GBM tumor growth by regulating YY1/SLC1A5 pathway.</p><p><strong>Conclusion: </strong>Silibinin plays an anti-tumor role in GBM process, which may be achieved via inhibiting YY1/SLC1A5 pathway.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220333"},"PeriodicalIF":2.1,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973575","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}

{"title":"Brain expression profiles of two <i>SCN1A</i> antisense RNAs in children and adolescents with epilepsy.","authors":"Marius Frederik Schneider, Miriam Vogt, Johanna Scheuermann, Veronika Müller, Antje H L Fischer-Hentrich, Thomas Kremer, Sebastian Lugert, Friedrich Metzger, Manfred Kudernatsch, Gerhard Kluger, Till Hartlieb, Soheyl Noachtar, Christian Vollmar, Mathias Kunz, Jörg Christian Tonn, Roland Coras, Ingmar Blümcke, Claudia Pace, Florian Heinen, Christoph Klein, Heidrun Potschka, Ingo Borggraefe","doi":"10.1515/tnsci-2022-0330","DOIUrl":"10.1515/tnsci-2022-0330","url":null,"abstract":"<p><strong>Objective: </strong>Heterozygous mutations within the voltage-gated sodium channel α subunit (<i>SCN1A</i>) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of <i>SCN1A</i> are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches.</p><p><strong>Methods: </strong>We investigated <i>SCN1A</i> mRNA expression and expression of two <i>SCN1A</i> related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against <i>SCN1A</i> specific antisense RNAs on <i>SCN1A</i> expression was tested.</p><p><strong>Results: </strong>The <i>SCN1A</i> related antisense RNAs <i>SCN1A</i>-dsAS (downstream antisense, RefSeq identifier: NR_110598) and <i>SCN1A</i>-usAS (upstream AS, <i>SCN1A</i>-AS, RefSeq identifier: NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA <i>SCN1A</i>-usAS with <i>SCN1A</i> mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against <i>SCN1A</i>-dsAS was associated with a significant enhancement of <i>SCN1A</i> mRNA expression and reduction in <i>SCN1A</i>-dsAS transcripts.</p><p><strong>Conclusion: </strong>These findings support the role of <i>SCN1A</i>-dsAS in the suppression of <i>SCN1A</i> mRNA generation. Considering the haploinsufficiency in genetic <i>SCN1A</i> related DS, <i>SCN1A</i>-dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance <i>SCN1A</i> expression in DS.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220330"},"PeriodicalIF":1.8,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10811528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571447","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}

{"title":"Functional connectivity in ADHD children doing Go/No-Go tasks: An fMRI systematic review and meta-analysis.","authors":"Sihyong J Kim, Onur Tanglay, Elizabeth H N Chong, Isabella M Young, Rannulu D Fonseka, Hugh Taylor, Peter Nicholas, Stephane Doyen, Michael E Sughrue","doi":"10.1515/tnsci-2022-0299","DOIUrl":"10.1515/tnsci-2022-0299","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders diagnosed in childhood. Two common features of ADHD are impaired behavioural inhibition and sustained attention. The Go/No-Go experimental paradigm with concurrent functional magnetic resonance imaging (fMRI) scanning has previously revealed important neurobiological correlates of ADHD such as the supplementary motor area and the prefrontal cortex. The coordinate-based meta-analysis combined with quantitative techniques, such as activation likelihood estimate (ALE) generation, provides an unbiased and objective method of summarising these data to understand the brain network architecture and connectivity in ADHD children. Go/No-Go task-based fMRI studies involving children and adolescent subjects were selected. Coordinates indicating foci of activation were collected to generate ALEs using threshold values (voxel-level: <i>p</i> < 0.001; cluster-level: <i>p</i> < 0.05). ALEs were matched to one of seven canonical brain networks based on the cortical parcellation scheme derived from the Human Connectome Project. Fourteen studies involving 457 children met the eligibility criteria. No significant convergence of Go/No-Go related brain activation was found for ADHD groups. Three significant ALE clusters were detected for brain activation relating to controls or ADHD < controls. Significant clusters were related to specific areas of the default mode network (DMN). Network-based analysis revealed less extensive DMN, dorsal attention network, and limbic network activation in ADHD children compared to controls. The presence of significant ALE clusters may be due to reduced homogeneity in the selected sample demographic and experimental paradigm. Further investigations regarding hemispheric asymmetry in ADHD subjects would be beneficial.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220299"},"PeriodicalIF":2.1,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973574","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}

{"title":"Revealing key role of T cells in neurodegenerative diseases, with potential to develop new targeted therapies.","authors":"Haofuzi Zhang, Xiaofan Jiang","doi":"10.1515/tnsci-2022-0329","DOIUrl":"10.1515/tnsci-2022-0329","url":null,"abstract":"<p><p>David M. Holtzman and his team at the University of Washington School of Medicine have made breakthroughs in their research on neurodegenerative diseases. They discovered that the infiltration of T cells into the brain, instigated by activated microglia, is a critical factor in the progression of tauopathy. The groundbreaking findings were published in Nature on March 8, 2023. This research delineates a pivotal immune hub linked to tauopathy and neurodegeneration; a complex interplay involving activated microglia and T cell responses. This discovery could potentially become a target for developing therapeutic interventions for Alzheimer's disease and primary neurodegeneration.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220329"},"PeriodicalIF":1.8,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404519","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}

{"title":"The BET inhibitor apabetalone decreases neuroendothelial proinflammatory activation <i>in vitro</i> and in a mouse model of systemic inflammation.","authors":"Sylwia Wasiak, Li Fu, Emily Daze, Dean Gilham, Brooke D Rakai, Stephanie C Stotz, Laura M Tsujikawa, Chris D Sarsons, Deborah Studer, Kristina D Rinker, Ravi Jahagirdar, Norman C W Wong, Michael Sweeney, Jan O Johansson, Ewelina Kulikowski","doi":"10.1515/tnsci-2022-0332","DOIUrl":"10.1515/tnsci-2022-0332","url":null,"abstract":"<p><p>Brain vascular inflammation is characterized by endothelial activation and immune cell recruitment to the blood vessel wall, potentially causing a breach in the blood - brain barrier, brain parenchyma inflammation, and a decline of cognitive function. The clinical-stage small molecule, apabetalone, reduces circulating vascular endothelial inflammation markers and improves cognitive scores in elderly patients by targeting epigenetic regulators of gene transcription, bromodomain and extraterminal proteins. However, the effect of apabetalone on cytokine-activated brain vascular endothelial cells (BMVECs) is unknown. Here, we show that apabetalone treatment of BMVECs reduces hallmarks of <i>in vitro</i> endothelial activation, including monocyte chemoattractant protein-1 (MCP-1) and RANTES chemokine secretion, cell surface expression of endothelial cell adhesion molecule VCAM-1, as well as endothelial capture of THP-1 monocytes in static and shear stress conditions. Apabetalone pretreatment of THP-1 downregulates cell surface expression of chemokine receptors CCR1, CCR2, and CCR5, and of the VCAM-1 cognate receptor, integrin α4. Consequently, apabetalone reduces THP-1 chemoattraction towards soluble CCR ligands MCP-1 and RANTES, and THP-1 adhesion to activated BMVECs. In a mouse model of brain inflammation, apabetalone counters lipopolysaccharide-induced transcription of endothelial and myeloid cell markers, consistent with decreased neuroendothelial inflammation. In conclusion, apabetalone decreases proinflammatory activation of brain endothelial cells and monocytes <i>in vitro</i> and in the mouse brain during systemic inflammation.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220332"},"PeriodicalIF":2.1,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466864","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}

{"title":"Carthamin yellow attenuates brain injury in a neonatal rat model of ischemic-hypoxic encephalopathy by inhibiting neuronal ferroptosis in the hippocampus.","authors":"Yuanyu Zhou, Yuebin Wang, Xiaoqing Wu, Junjie Wu, Jianhui Yan, Wei Su","doi":"10.1515/tnsci-2022-0331","DOIUrl":"10.1515/tnsci-2022-0331","url":null,"abstract":"<p><p>Hypoxic-ischemic encephalopathy (HIE) is a common neurological disorder characterized by ischemia and hypoxia in the perinatal period, which seriously affects the growth and development of newborns. To date, there is no specific drug for the treatment of HIE. Previous studies have shown that ferroptosis plays an important role in the pathogenesis of HIE. Carthamin yellow (CY) is believed to have antioxidant and anti-inflammatory effects. However, no studies have reported the role of CY in ferroptosis in HIE <i>in vivo</i> until now. The aim of this study was to investigate the effect and mechanism of CY on HIE <i>in vivo</i> and to provide an experimental basis for the clinical treatment of HIE. The results demonstrated that CY increased the expression of NeuN in the neonatal rat hypoxic-ischemic brain damage (HIBD) model. Further exploration revealed that CY increased the expression of glutathione peroxidase 4 and ferritin heavy chain 1 while it decreased the expression of PTGS2 and ACSL2. Moreover, CY decreased malondialdehyde expression and increased superoxide dismutase and glutathione expression <i>in vivo</i>. The findings also indicated that CY downregulated the expression of Nrf2 and Keap-1. In conclusion, this study demonstrated that CY attenuated brain injury in an experimental HIBD model, potentially by alleviating hippocampal neuronal ferroptosis through inhibition of the Nrf2/Keap-1 signaling pathway. These findings provide a novel therapeutic strategy for the clinical treatment of HIE.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220331"},"PeriodicalIF":2.1,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492235","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}