ASN NEUROPub Date : 2023-01-01DOI: 10.1177/17590914231155976
G C Nascimento, M Bortolanza, A Bribian, G C Leal-Luiz, R Raisman-Vozari, L López-Mascaraque, E Del-Bel
{"title":"Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline.","authors":"G C Nascimento, M Bortolanza, A Bribian, G C Leal-Luiz, R Raisman-Vozari, L López-Mascaraque, E Del-Bel","doi":"10.1177/17590914231155976","DOIUrl":"https://doi.org/10.1177/17590914231155976","url":null,"abstract":"<p><strong>Summary statement: </strong>NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231155976"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/1f/10.1177_17590914231155976.PMC10084551.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9566783","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}
ASN NEUROPub Date : 2022-05-01DOI: 10.1177/17590914221102068
M. Dragić, Katarina Mihajlović, Marija Adzic, Marija Jakovljevic, M. Z. Kontić, N. Mitrović, Danijela Laketa, I. Lavrnja, M. Kipp, I. Grković, N. Nedeljkovic
{"title":"Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro","authors":"M. Dragić, Katarina Mihajlović, Marija Adzic, Marija Jakovljevic, M. Z. Kontić, N. Mitrović, Danijela Laketa, I. Lavrnja, M. Kipp, I. Grković, N. Nedeljkovic","doi":"10.1177/17590914221102068","DOIUrl":"https://doi.org/10.1177/17590914221102068","url":null,"abstract":"Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regulation of NTPDase2 by inflammatory mediators in primary astrocytes and oligodendroglial cell line OLN93. In physiological conditions, NTPDase2 protein was most abundant in the hippocampus, where it was found in fibrous astrocytes and synaptic endings in the synaptic-rich hippocampal layers. In TMT-induced neurodegeneration, NTPDase2-mRNA acutely decreased at 2-dpi and then gradually recovered to the control level at 7-dpi and 21-dpi. As determined by immunohistochemistry and double immunofluorescence, the decrease was most pronounced in the dentate gyrus (DG), where NTPDase2 withdrew from the synaptic boutons in the polymorphic layer of DG, whereas the recovery of the expression was most profound in the subgranular layer. Concerning the regulation of NTPDase2 gene expression, proinflammatory cytokines IL-6, IL-1β, TNFα, and IFNγ negatively regulated the expression of NTPDase2 in OLN93 cells, while did not altering the expression in primary astrocytes. Different cell-intrinsic stressors, such as depletion of intracellular energy store, oxidative stress, endoplasmic reticulum stress, and activation of protein kinase C, also massively disturbed the expression of the NTPDase2 gene. Together, our results suggest that the expression and the activity of NTPDase2 transiently cease in neurodegeneration and brain injury, most likely as a part of the acute adaptive response designed to promote cell defense, survival, and recovery.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46001693","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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221112352
Jeffrey L Dupree, Pablo M Paez, Seema K Tiwari-Woodruff, Travis T Denton, Kenneth Hensley, Christina G Angeliu, Anne I Boullerne, Sergey Kalinin, Sophia Egge, Veronica T Cheli, Giancarlo Denaroso, Kelley C Atkinson, Micah Feri, Douglas L Feinstein
{"title":"Lanthionine Ketimine Ethyl Ester Accelerates Remyelination in a Mouse Model of Multiple Sclerosis.","authors":"Jeffrey L Dupree, Pablo M Paez, Seema K Tiwari-Woodruff, Travis T Denton, Kenneth Hensley, Christina G Angeliu, Anne I Boullerne, Sergey Kalinin, Sophia Egge, Veronica T Cheli, Giancarlo Denaroso, Kelley C Atkinson, Micah Feri, 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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221131452
Jzmín Soto-Verdugo, Janisse Siva-Parra, Luisa C Hernández-Kelly, Arturo Ortega
{"title":"Acute Manganese Exposure Modifies the Translation Machinery <i>via</i> PI3K/Akt Signaling in Glial Cells.","authors":"Jzmín Soto-Verdugo, Janisse Siva-Parra, Luisa C Hernández-Kelly, Arturo Ortega","doi":"10.1177/17590914221131452","DOIUrl":"https://doi.org/10.1177/17590914221131452","url":null,"abstract":"<p><strong>Summary statement: </strong>We demonstrate herein that short-term exposure of radial glia cells to Manganese, a neurotoxic metal, induces an effect on protein synthesis, altering the protein <i>repertoire</i> of these cells.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221131452"},"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/5a/2d/10.1177_17590914221131452.PMC9551334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33492373","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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914211073276
Jean-Pierre Clément, Laila Al-Alwan, Stephen D Glasgow, Avya Stolow, Yi Ding, Thaiany Quevedo Melo, Anouar Khayachi, Yumin Liu, Markus Hellmund, Rainer Haag, Austen J Milnerwood, Peter Grütter, Timothy E Kennedy
{"title":"Dendritic Polyglycerol Amine: An Enhanced Substrate to Support Long-Term Neural Cell Culture.","authors":"Jean-Pierre Clément, Laila Al-Alwan, Stephen D Glasgow, Avya Stolow, Yi Ding, Thaiany Quevedo Melo, Anouar Khayachi, Yumin Liu, Markus Hellmund, Rainer Haag, Austen J Milnerwood, Peter Grütter, Timothy E Kennedy","doi":"10.1177/17590914211073276","DOIUrl":"https://doi.org/10.1177/17590914211073276","url":null,"abstract":"<p><p>Long-term stable cell culture is a critical tool to better understand cell function. Most adherent cell culture models require a polymer substrate coating of poly-lysine or poly-ornithine for the cells to adhere and survive. However, polypeptide-based substrates are degraded by proteolysis and it remains a challenge to maintain healthy cell cultures for extended periods of time. Here, we report the development of an enhanced cell culture substrate based on a coating of dendritic polyglycerol amine (dPGA), a non-protein macromolecular biomimetic of poly-lysine, to promote the adhesion and survival of neurons in cell culture. We show that this new polymer coating provides enhanced survival, differentiation and long-term stability for cultures of primary neurons or neurons derived from human induced pluripotent stem cells (hiPSCs). Atomic force microscopy analysis provides evidence that greater nanoscale roughness contributes to the enhanced capacity of dPGA-coated surfaces to support cells in culture. We conclude that dPGA is a cytocompatible, functionally superior, easy to use, low cost and highly stable alternative to poly-cationic polymer cell culture substrate coatings such as poly-lysine and poly-ornithine. <b>Summary statement</b>Here, we describe a novel dendritic polyglycerol amine-based substrate coating, demonstrating superior performance compared to current polymer coatings for long-term culture of primary neurons and neurons derived from induced pluripotent stem cells.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211073276"},"PeriodicalIF":4.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816465","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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221102065
Jessy V. van Asperen, P. Robe, Elly M. Hol
{"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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221102075
Ernesto Alberto Rendón-Ochoa, Montserrat Padilla-Orozco, Vladimir Melesio Calderon, Victor Hugo Avilés-Rosas, Omar Hernández-González, Teresa Hernández-Flores, María Belén Perez-Ramirez, Marcela Palomero-Rivero, Elvira Galarraga, José Bargas
{"title":"Dopamine D<sub>2</sub> and Adenosine A<sub>2A</sub> Receptors Interaction on Ca<sup>2+</sup> Current Modulation in a Rodent Model of Parkinsonism.","authors":"Ernesto Alberto Rendón-Ochoa, Montserrat Padilla-Orozco, Vladimir Melesio Calderon, Victor Hugo Avilés-Rosas, Omar Hernández-González, Teresa Hernández-Flores, María Belén Perez-Ramirez, Marcela Palomero-Rivero, Elvira Galarraga, José Bargas","doi":"10.1177/17590914221102075","DOIUrl":"https://doi.org/10.1177/17590914221102075","url":null,"abstract":"<p><strong>Summary statement: </strong>A<sub>2A</sub> receptor required previous D<sub>2</sub> receptor activation to modulate Ca<sup>2+</sup> currents. Istradefylline decreases pramipexole modulation on Ca<sup>2+</sup> currents. Istradefylline reduces A<sub>2A</sub> + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221102075"},"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/37/f9/10.1177_17590914221102075.PMC9178983.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40339818","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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221093257
Sanja Dimitrijevic, Biljana Jekic, Suzana Cvjeticanin, Aleksandra Tucovic, Tamara Filipovic, Ivana Novaković, Bojana Ivić, Dimitrije Nikolic
{"title":"KCC2 rs2297201 Gene Polymorphism Might be a Predictive Genetic Marker of Febrile Seizures.","authors":"Sanja Dimitrijevic, Biljana Jekic, Suzana Cvjeticanin, Aleksandra Tucovic, Tamara Filipovic, Ivana Novaković, Bojana Ivić, 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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221145105
Ye Man Tang, Nisha S Pulimood, Stefano Stifani
{"title":"Comparing the Characteristics of Microglia Preparations Generated Using Different Human iPSC-Based Differentiation Methods to Model Neurodegenerative Diseases.","authors":"Ye Man Tang, Nisha S Pulimood, 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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221106510
{"title":"Corrigendum to miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology.","authors":"","doi":"10.1177/17590914221106510","DOIUrl":"https://doi.org/10.1177/17590914221106510","url":null,"abstract":"CCAAT/enhancer-binding Lipopolysaccharide.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221106510"},"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/53/8b/10.1177_17590914221106510.PMC9393660.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40617721","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}