ASN NEURO最新文献

{"title":"Lanthionine Ketimine Ethyl Ester Accelerates Remyelination in a Mouse Model of Multiple Sclerosis.","authors":"Jeffrey L Dupree,&nbsp;Pablo M Paez,&nbsp;Seema K Tiwari-Woodruff,&nbsp;Travis T Denton,&nbsp;Kenneth Hensley,&nbsp;Christina G Angeliu,&nbsp;Anne I Boullerne,&nbsp;Sergey Kalinin,&nbsp;Sophia Egge,&nbsp;Veronica T Cheli,&nbsp;Giancarlo Denaroso,&nbsp;Kelley C Atkinson,&nbsp;Micah Feri,&nbsp;Douglas L Feinstein","doi":"10.1177/17590914221112352","DOIUrl":"https://doi.org/10.1177/17590914221112352","url":null,"abstract":"<p><p>Although over 20 disease modifying therapies are approved to treat Multiple Sclerosis (MS), these do not increase remyelination of demyelinated axons or mitigate axon damage. Previous studies showed that lanthionine ketenamine ethyl ester (LKE) reduces clinical signs in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS and increased maturation of oligodendrocyte (OL) progenitor cells (OPCs) <i>in vitro</i>. In the current study, we used the cuprizone (CPZ) demyelination model of MS to test if LKE could increase remyelination. The corpus callosum (CC) and somatosensory cortex was examined by immunohistochemistry (IHC), electron microscopy and for mRNA expression changes in mice provided 5 weeks of CPZ diet followed by 2 weeks of normal diet in the presence of LKE or vehicle. A significant increase in the number of myelinated axons, and increased myelin thickness was observed in the CC of LKE-treated groups compared to vehicle-treated groups. LKE also increased myelin basic protein and proteolipid protein expression in the CC and cortex, and increased the number of mature OLs in the cortex. In contrast, LKE did not increase the percentage of proliferating OPCs suggesting effects on OPC survival and differentiation but not proliferation. The effects of LKE on OL maturation and remyelination were supported by similar changes in their relative mRNA levels. Interestingly, LKE did not have significant effects on GFAP or Iba1 immunostaining or mRNA levels. These findings suggest that remyelinating actions of LKE can potentially be formulated to induce remyelination in neurological diseases associated with demyelination including MS.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221112352"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/dd/10.1177_17590914221112352.PMC9272172.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10345469","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":"GFAP Alternative Splicing and the Relevance for Disease – A Focus on Diffuse Gliomas","authors":"Jessy V. van Asperen, P. Robe, Elly M. Hol","doi":"10.1177/17590914221102065","DOIUrl":"https://doi.org/10.1177/17590914221102065","url":null,"abstract":"Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocytes and neural stem cells, and their malignant analogues in glioma. Since the discovery of the protein 50 years ago, multiple alternative splice variants of the GFAP gene have been discovered, leading to different GFAP isoforms. In this review, we will describe GFAP isoform expression from gene to protein to network, taking the canonical isoforms GFAPα and the main alternative variant GFAPδ as the starting point. We will discuss the relevance of studying GFAP and its isoforms in disease, with a specific focus on diffuse gliomas.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41336085","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}

{"title":"KCC2 rs2297201 Gene Polymorphism Might be a Predictive Genetic Marker of Febrile Seizures.","authors":"Sanja Dimitrijevic,&nbsp;Biljana Jekic,&nbsp;Suzana Cvjeticanin,&nbsp;Aleksandra Tucovic,&nbsp;Tamara Filipovic,&nbsp;Ivana Novaković,&nbsp;Bojana Ivić,&nbsp;Dimitrije Nikolic","doi":"10.1177/17590914221093257","DOIUrl":"https://doi.org/10.1177/17590914221093257","url":null,"abstract":"<p><p><b>Introduction:</b> Febrile seizures (FS) are the most common neurological disease in childhood. The etiology of FS is the subject of numerous studies including studies regarding genetic predisposition. <b>Aim:</b> The aim of the study was to analyze the association of <i>TRPV1</i> rs222747 and <i>KCC2</i> rs2297201 gene polymorphisms with the occurrence of FS. <b>Materials and Methods:</b> The study included 112 patients diagnosed with FS classified as simple febrile seizures (SFS) or complex febrile seizures (CFS). We analyzed selected polymorphisms of <i>KCC2</i> and <i>TRPV1</i> genes using the Real-time PCR method. <b>Results:</b> The CT and TT genotypes of the rs2297201 polymorphism of the <i>KCC2</i> gene are significantly more common in the group of children with FS than the control group (<i>p</i> = .002) as well as the allele T of this polymorphism (<i>p</i> = .045). Additionally, genotypes CT and TT of the rs2297201 polymorphism of the <i>KCC2</i> gene were more frequent in the group of children with CFS compared to the control group (<i>p</i> < .001). Different genotypes and alleles of the rs222747 <i>TRPV1</i> gene polymorphism were not associated with the occurrence of febrile seizures or epilepsy, nor were associated with the occurrence of a particular type of febrile seizure (<i>p</i> = .252). <b>Conclusion:</b> These results indicate that the CT and TT genotypes, as well as the T allele of rs2297201 polymorphism of the <i>KCC2</i> gene, could be a predisposing factor for the FS, as well as the occurrence of CFS.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221093257"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/ce/10.1177_17590914221093257.PMC9016559.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9254553","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":"Comparing the Characteristics of Microglia Preparations Generated Using Different Human iPSC-Based Differentiation Methods to Model Neurodegenerative Diseases.","authors":"Ye Man Tang,&nbsp;Nisha S Pulimood,&nbsp;Stefano Stifani","doi":"10.1177/17590914221145105","DOIUrl":"https://doi.org/10.1177/17590914221145105","url":null,"abstract":"<p><p>As the resident immune cells of the healthy nervous system, homeostatic microglia can rapidly become activated in response to injury/disease. Dysregulated microglia activation is a hallmark of nervous system disorders including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. The elucidation of the biological and pathological roles of microglia has recently benefitted from the development of microglia-like cells using human induced pluripotent stem cell (iPSC)-based approaches. The success of iPSC-derived microglia preparations as a disease-relevant model system depends on their representation of the <i>in vivo</i> spatial and temporal heterogeneity of microglia under pathological conditions. Little is currently known about the potential of human iPSC-derived microglia generated using different methods for the study of neurodegenerative diseases. We compared the transcriptomes of human iPSC-derived microglia generated using two frequently used <i>in vitro</i> differentiation methods to determine whether separate strategies can generate microglia with distinct transcriptional signatures <i>in vitro</i>. We show that microglia derived using different differentiation methods display distinct maturation characteristics after equivalent times in culture. We also reveal that iPSC-derived microglia preparations generated using these two methods are composed of different subpopulations with transcriptomic signatures resembling those of <i>in vivo</i> regionally distinct microglia subtypes, specifically white-matter and gray-matter microglia. These findings highlight the need to better characterize the subtype composition of each microglia preparation prior to its use to model neurodegenerative diseases.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221145105"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/86/10.1177_17590914221145105.PMC9761225.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412661","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":"Identification of microRNA-mRNA regulatory network associated with oxidative DNA damage in human astrocytes.","authors":"Chukwumaobim Daniel Nwokwu,&nbsp;Adam Y Xiao,&nbsp;Lynn Harrison,&nbsp;Gergana G Nestorova","doi":"10.1177/17590914221101704","DOIUrl":"https://doi.org/10.1177/17590914221101704","url":null,"abstract":"<p><p>The high lipid content of the brain, coupled with its heavy oxygen dependence and relatively weak antioxidant system, makes it highly susceptible to oxidative DNA damage that contributes to neurodegeneration. This study is aimed at identifying specific ROS-responsive miRNAs that modulate the expression and activity of the DNA repair proteins in human astrocytes, which could serve as potential biomarkers and lead to the development of targeted therapeutic strategies for neurological diseases. Oxidative DNA damage was established after treatment of human astrocytes with 10μM sodium dichromate for 16 h. Comet assay analysis indicated a significant increase in oxidized guanine lesions. RT-qPCR and ELISA assays confirmed that sodium dichromate reduced the mRNA and protein expression levels of the human base-excision repair enzyme, 8-deoxyguanosine DNA glycosylase 1 (hOGG1). Small RNAseq data were generated on an Ion Torrent™ system and the differentially expressed miRNAs were identified using Partek Flow® software. The biologically significant miRNAs were selected using miRNet 2.0. Oxidative-stress-induced DNA damage was associated with a significant decrease in miRNA expression: 231 downregulated miRNAs and 2 upregulated miRNAs (p < 0.05; >2-fold). In addition to identifying multiple miRNA-mRNA pairs involved in DNA repair processes, this study uncovered a novel miRNA-mRNA pair interaction: miR-1248:OGG1. Inhibition of miR-1248 via the transfection of its inhibitor restored the expression levels of hOGG1. Therefore, targeting the identified microRNA candidates could ameliorate the nuclear DNA damage caused by the brain's exposure to mutagens, reduce the incidence and improve the treatment of cancer and neurodegenerative disorders.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221101704"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/99/10.1177_17590914221101704.PMC9118907.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10617088","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 2021","authors":"","doi":"10.1177/17590914221076664","DOIUrl":"https://doi.org/10.1177/17590914221076664","url":null,"abstract":"","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"57 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41245735","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}

{"title":"Hepatoma Derived Growth Factor Enhances Oligodendrocyte Genesis from Subventricular Zone Precursor Cells","authors":"Yutong Li, Nicole L Dittmann, A. Watson, M. M. D. de Almeida, T. Footz, Anastassia Voronova","doi":"10.1177/17590914221086340","DOIUrl":"https://doi.org/10.1177/17590914221086340","url":null,"abstract":"Oligodendrocytes, the myelinating cells of the central nervous system (CNS), perform vital functions in neural protection and communication, as well as cognition. Enhanced production of oligodendrocytes has been identified as a therapeutic approach for neurodegenerative and neurodevelopmental disorders. In the postnatal brain, oligodendrocytes are generated from the neural stem and precursor cells (NPCs) in the subventricular zone (SVZ) and parenchymal oligodendrocyte precursor cells (OPCs). Here, we demonstrate exogenous Hepatoma Derived Growth Factor (HDGF) enhances oligodendrocyte genesis from murine postnatal SVZ NPCs in vitro without affecting neurogenesis or astrogliogenesis. We further show that this is achieved by increasing proliferation of both NPCs and OPCs, as well as OPC differentiation into oligodendrocytes. In vivo results demonstrate that intracerebroventricular infusion of HDGF leads to increased oligodendrocyte genesis from SVZ NPCs, as well as OPC proliferation. Our results demonstrate a novel role for HDGF in regulating SVZ precursor cell proliferation and oligodendrocyte differentiation. Summary Statement Hepatoma derived growth factor (HDGF) is produced by neurons. However, its role in the central nervous system is largely unknown. We demonstrate HDGF enhances i) oligodendrocyte formation from subventricular zone neural stem cells, and ii) oligodendrocyte precursor proliferation in vitro and in vivo.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47952735","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}

{"title":"New Target for Prevention and Treatment of Neuroinflammation: Microglia Iron Accumulation and Ferroptosis","authors":"Shunfeng Liu, Xueyuan Gao, Shouhong Zhou","doi":"10.1177/17590914221133236","DOIUrl":"https://doi.org/10.1177/17590914221133236","url":null,"abstract":"Microglia play an important role in maintaining central nervous system homeostasis and are the major immune cells in the brain. In response to internal or external inflammatory stimuli, microglia are activated and release numerous inflammatory factors, thus leading to neuroinflammation. Inflammation and microglia iron accumulation promote each other and jointly promote the progression of neuroinflammation. Inhibiting microglia iron accumulation prevents neuroinflammation. Ferroptosis is an iron-dependent phospholipid peroxidation-driven type of cell death regulation. Cell iron accumulation causes the peroxidation of cell membrane phospholipids and damages the cell membrane. Ultimately, this process leads to cell ferroptosis. Iron accumulation or phospholipid peroxidation in microglia releases a large number of inflammatory factors. Thus, inhibiting microglia ferroptosis may be a new target for the prevention and treatment of neuroinflammation.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44965767","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}

{"title":"Disruption of Synaptic Transmission in the Bed Nucleus of the Stria Terminalis Reduces Seizure-Induced Death in DBA/1 Mice and Alters Brainstem E/I Balance.","authors":"Maya Xia,&nbsp;Benjamin Owen,&nbsp;Jeremy Chiang,&nbsp;Alyssa Levitt,&nbsp;Katherine Preisinger,&nbsp;Wen Wei Yan,&nbsp;Ragan Huffman,&nbsp;William P Nobis","doi":"10.1177/17590914221103188","DOIUrl":"https://doi.org/10.1177/17590914221103188","url":null,"abstract":"<p><p>Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Accumulating evidence from recent human studies and animal models suggests that seizure-related respiratory arrest may be important for initiating cardiorespiratory arrest and death. Prior evidence suggests that apnea onset can coincide with seizure spread to the amygdala and that stimulation of the amygdala can reliably induce apneas in epilepsy patients, potentially implicating amygdalar regions in seizure-related respiratory arrest and subsequent postictal hypoventilation and cardiorespiratory death. This study aimed to determine if an extended amygdalar structure, the dorsal bed nucleus of the stria terminalis (dBNST), is involved in seizure-induced respiratory arrest (S-IRA) and death using DBA/1 mice, a mouse strain which has audiogenic seizures (AGS) and a high incidence of postictal respiratory arrest and death. The presence of S-IRA significantly increased c-Fos expression in the dBNST of DBA/1 mice. Furthermore, disruption of synaptic output from the dBNST via viral-induced tetanus neurotoxin (TeNT) significantly improved survival following S-IRA in DBA/1 mice without affecting baseline breathing or hypercapnic (HCVR) and hypoxic ventilatory response (HVR). This disruption in the dBNST resulted in changes to the balance of excitatory/inhibitory (E/I) synaptic events in the downstream brainstem regions of the lateral parabrachial nucleus (PBN) and the periaqueductal gray (PAG). These findings suggest that the dBNST is a potential subcortical forebrain site necessary for the mediation of S-IRA, potentially through its outputs to brainstem respiratory regions.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221103188"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/65/10.1177_17590914221103188.PMC9136462.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10694884","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":"Multispectral LEDs Eliminate Lipofuscin-Associated Autofluorescence for Immunohistochemistry and CD44 Variant Detection by in Situ Hybridization in Aging Human, non-Human Primate, and Murine Brain.","authors":"Philip A Adeniyi, Katie-Anne Fopiano, Fatima Banine, Mariel Garcia, Xi Gong, C Dirk Keene, Larry S Sherman, Zsolt Bagi, Stephen A Back","doi":"10.1177/17590914221123138","DOIUrl":"10.1177/17590914221123138","url":null,"abstract":"<p><p>A major limitation of mechanistic studies in aging brains is the lack of routine methods to robustly visualize and discriminate the cellular distribution of tissue antigens using fluorescent immunohistochemical multi-labeling techniques. Although such approaches are routine in non-aging brains, they are not consistently feasible in the aging brain due to the progressive accumulation of autofluorescent pigments, particularly lipofuscin, which strongly excite and emit over a broad spectral range. Consequently, aging research has relied upon colorimetric antibody techniques, where discrimination of tissue antigens is often challenging. We report the application of a simple, reproducible, and affordable protocol using multispectral light-emitting diodes (mLEDs) exposure for the reduction/elimination of lipofuscin autofluorescence (LAF) in aging brain tissue from humans, non-human primates, and mice. The mLEDs lamp has a broad spectral range that spans from the UV to infrared range and includes spectra in the violet/blue and orange/red. After photo quenching, the LAF level was markedly reduced when the tissue background fluorescence before and after mLEDs exposure was compared (p < 0.0001) across the spectral range. LAF elimination was estimated at 95 ± 1%. This approach permitted robust specific fluorescent immunohistochemical co-visualization of commonly studied antigens in aging brains. We also successfully applied this method to specifically visualize CD44 variant expression in aging human cerebral white matter using RNAscope fluorescent in-situ hybridization. Photo quenching provides an attractive means to accelerate progress in aging research by increasing the number of molecules that can be topologically discriminated by fluorescence detection in brain tissue from normative or pathological aging.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221123138"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/82/10.1177_17590914221123138.PMC9520168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10820881","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}