ASN NEURO最新文献

{"title":"miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology.","authors":"Alexander D Walsh,&nbsp;Linda T Nguyen,&nbsp;Michele D Binder","doi":"10.1177/1759091420981182","DOIUrl":"https://doi.org/10.1177/1759091420981182","url":null,"abstract":"<p><p>Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"1759091420981182"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091420981182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25313702","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":"B and T Lymphocyte Densities Remain Stable With Age in Human Cortex.","authors":"Kacey Berry,&nbsp;Daniela S Farias-Itao,&nbsp;Lea T Grinberg,&nbsp;Edward D Plowey,&nbsp;Julie A Schneider,&nbsp;Roberta D Rodriguez,&nbsp;Claudia K Suemoto,&nbsp;Marion S Buckwalter","doi":"10.1177/17590914211018117","DOIUrl":"https://doi.org/10.1177/17590914211018117","url":null,"abstract":"<p><p>One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44-96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211018117"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211018117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38955198","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":"SAN 2019 Abstract Book for ASN Neuro MAY 2020.","authors":"","doi":"10.1177/1759091420979851","DOIUrl":"https://doi.org/10.1177/1759091420979851","url":null,"abstract":"There","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"1759091420979851"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091420979851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25492290","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":"Reviewer List 2020.","authors":"","doi":"10.1177/1759091421994019","DOIUrl":"https://doi.org/10.1177/1759091421994019","url":null,"abstract":"","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"1759091421994019"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091421994019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25332549","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":"Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity.","authors":"Yuanyuan Ran,&nbsp;Lin Ye,&nbsp;Zitong Ding,&nbsp;Fuhai Gao,&nbsp;Shuiqing Yang,&nbsp;Boyan Fang,&nbsp;Zongjian Liu,&nbsp;Jianing Xi","doi":"10.1177/17590914211022888","DOIUrl":"https://doi.org/10.1177/17590914211022888","url":null,"abstract":"<p><p>Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke <i>in vivo</i> model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin's direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211022888"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211022888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39089040","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":"2021 ASN Virtual Meeting Abstracts.","authors":"","doi":"10.1177/17590914211039028","DOIUrl":"https://doi.org/10.1177/17590914211039028","url":null,"abstract":"","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"13 ","pages":"17590914211039028"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9354664","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":"Sex Effect on Cardiac Damage in Mice With Experimental Autoimmune Encephalomyelitis.","authors":"Ruixia Wu,&nbsp;Yue Su,&nbsp;Quan Yuan,&nbsp;Linlin Li,&nbsp;Jimusi Wuri,&nbsp;Xiaoxuan Liu,&nbsp;Tao Yan","doi":"10.1177/1759091421991771","DOIUrl":"https://doi.org/10.1177/1759091421991771","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Recent clinical study suggested that MS patient exhibited acute heart failure. Further, 12-lead electrocardiographic study showed a longer QTc interval in both MS patient and experimental autoimmune encephalomyelitis (EAE) Lewis rat. However, there is limited study regarding the effect of sex on cardiac injury in EAE. To our knowledge, sex effect on cardiac damage in mice with EAE has not yet been published. Herein, we examined the role of the immune system in mediating cardiac dysfunction after EAE in female and male mice. Neurological function was subsequently evaluated and cardiac function was assessed by echocardiography at multiple time points after EAE. EAE mice exhibited severe neurological deficit and significant cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 2 months after EAE induction. Meanwhile male EAE presented increased expression of the oxidative stress (e.g., nicotinamaide adenine dinucleotide phosphate oxidase-2; NOX-2) in heart, as well as cardiac hypertrophy, increased left ventricle (LV) mass and more severe cardiac fibrosis compared with male control mice. In addition, male EAE mice showed significantly increased cardiac canonical inflammatory mediator (e.g., monocyte chemoattractant protein-1; MCP-1, transforming growth factor-β; TGF-β and toll-like receptor 2; TLR-2) compared with female EAE mice at 2 months after EAE induction. In conclusion, EAE increases inflammatory factor expression and aggravates cardiac dysfunction in male mice compared with female mice, which may contribute to different cardiac outcome in EAE mice.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"1759091421991771"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1759091421991771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25332551","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":"<i>Aspergillus versicolor</i> Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.","authors":"Thatcher B Ladd,&nbsp;James A Johnson,&nbsp;Christen L Mumaw,&nbsp;Hendrik J Greve,&nbsp;Xiaoling Xuei,&nbsp;Ed Simpson,&nbsp;Mark A Barnes,&nbsp;Brett J Green,&nbsp;Tara L Croston,&nbsp;Chandrama Ahmed,&nbsp;Angela Lemons,&nbsp;Donald H Beezhold,&nbsp;Michelle L Block","doi":"10.1177/17590914211019886","DOIUrl":"https://doi.org/10.1177/17590914211019886","url":null,"abstract":"<p><p>Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated <i>Aspergillus versicolo</i>r (3 × 10⁵ spores), or viable <i>A. versicolo</i>r (3 × 10⁵ spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable <i>A. versicolo</i>r spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory (<i>Tnf and Il1b</i>) and glial activity (<i>Gdnf</i> and <i>Cxc3r1</i>) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of <i>A. versicolo</i>r exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of <i>Drd1</i>, <i>Penk</i>, and <i>Pdyn</i> mRNA expression was confirmed in the 4-week <i>A. versicolo</i>r exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated <i>A. versicolor</i> inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to <i>A. versicolo</i>r inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211019886"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211019886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39072006","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":"Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.","authors":"Audra York,&nbsp;Angela Everhart,&nbsp;Michael P Vitek,&nbsp;Kirby W Gottschalk,&nbsp;Carol A Colton","doi":"10.1177/17590914211019443","DOIUrl":"https://doi.org/10.1177/17590914211019443","url":null,"abstract":"<p><p>Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer's disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 (<i>RSAD1</i>) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. <i>APOE4</i> vs <i>APOE3</i> genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211019443"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17590914211019443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39090013","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":"Sevoflurane-Induced miR-211-5p Promotes Neuronal Apoptosis by Inhibiting Efemp2.","authors":"Yousu Shen,&nbsp;Tao Zhou,&nbsp;Xiaobing Liu,&nbsp;Yanlong Liu,&nbsp;Yaqi Li,&nbsp;Dewu Zeng,&nbsp;Wensheng Zhong,&nbsp;Mingsheng Zhang","doi":"10.1177/17590914211035036","DOIUrl":"https://doi.org/10.1177/17590914211035036","url":null,"abstract":"<p><p>Sevoflurane exposure can result in serious neurological side effects including neuronal apoptosis and cognitive impairment. Although the microRNA miR-211-5p is profoundly upregulated following sevoflurane exposure in neonatal rodent models, the impact of miR-211-5p on neuronal apoptosis and cognitive impairment postsevoflurane exposure has not yet been elucidated. Here, we found that sevoflurane upregulated miR-211-5p and downregulated EGF-Containing Fibulin Extracellular Matrix Protein 2 (Efemp2, Fibulin-4) levels in vitro and in vivo. Sevoflurane's effect on miR-211-5p expression was based on enhancing primary miR-211 transcription. miR-211-5p targets Efemp2's mRNA 3'-untranslated region, reducing Efemp2 expression. RNA immunoprecipitation revealed significant enrichment of the miR-211-5p:Efemp2 mRNA dyad in the RNA-induced silencing complex. miR-211-5p mimics downregulated Efemp2, leading to phosphorylation of Smad2 and Smad3, upregulation of pro-apoptotic Bim, and mitochondrial release of allograft inflammatory factor 1 and cytochrome C. In contrast, miR-211-5p hairpin inhibitor (AntimiR-211-5p) negatively regulated this apoptotic pathway and reduced neuronal apoptosis in an Efemp2-dependent manner. Sevoflurane-exposed mice administered AntimiR-211-5p displayed reduced cortical apoptosis levels and near-term cognitive impairment. In conclusion, sevoflurane-induced miR-211-5p promotes neuronal apoptosis via Efemp2 inhibition. Summary statement: This study revealed the significance of sevoflurane-induced increases in miR-211-5p on the promotion of neuronal apoptosis via inhibition of Efemp2 and its downstream targets.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211035036"},"PeriodicalIF":4.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/f9/10.1177_17590914211035036.PMC8819752.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586766","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}