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}
{"title":"EAAT1-dependent <i>slc1a3</i> Transcriptional Control depends on the Substrate Translocation Process.","authors":"Dinorah Hernández-Melchor, Leticia Ramírez-Martínez, Luis Cid, Cecilia Palafox-Gómez, Esther López-Bayghen, Arturo Ortega","doi":"10.1177/17590914221116574","DOIUrl":"https://doi.org/10.1177/17590914221116574","url":null,"abstract":"<p><strong>Summary statement: </strong>EAAT1/GLAST down-regulates its expression and function at the transcriptional level by activating a signaling pathway that includes PI3K, PKC and NF-κB, favoring the notion of an activity-dependent fine-tuning of glutamate recycling and its synaptic transactions through glial cells.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221116574"},"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/00/e9/10.1177_17590914221116574.PMC9340397.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40644897","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: 10.1177/17590914221135697
Estela M Muñoz
{"title":"Microglia in Circumventricular Organs: The Pineal Gland Example.","authors":"Estela M Muñoz","doi":"10.1177/17590914221135697","DOIUrl":"https://doi.org/10.1177/17590914221135697","url":null,"abstract":"<p><p>The circumventricular organs (CVOs) are unique areas within the central nervous system. They serve as a portal for the rest of the body and, as such, lack a blood-brain barrier. Microglia are the primary resident immune cells of the brain parenchyma. Within the CVOs, microglial cells find themselves continuously challenged and stimulated by local and systemic stimuli, even under steady-state conditions. Therefore, CVO microglia in their typical state often resemble the activated microglial forms found elsewhere in the brain as they are responding to pathological conditions or other stressors. In this review, I focus on the dynamics of CVO microglia, using the pineal gland as a specific CVO example. Data related to microglia heterogeneity in both homeostatic and unhealthy environments are presented and discussed, including those recently generated by using advanced single-cell and single-nucleus technology. Finally, perspectives in the CVO microglia field are also included.<b>Summary Statement</b>Microglia in circumventricular organs (CVOs) continuously adapt to react differentially to the diverse challenges they face. Herein, I discuss microglia heterogeneity in CVOs, including pineal gland. Further studies are needed to better understand microglia dynamics in these unique brain areas. .</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221135697"},"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/62/76/10.1177_17590914221135697.PMC9629557.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659536","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: 10.1177/17590914221101704
Chukwumaobim Daniel Nwokwu, Adam Y Xiao, Lynn Harrison, Gergana G Nestorova
{"title":"Identification of microRNA-mRNA regulatory network associated with oxidative DNA damage in human astrocytes.","authors":"Chukwumaobim Daniel Nwokwu, Adam Y Xiao, Lynn Harrison, 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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221086340
Yutong Li, Nicole L Dittmann, A. Watson, M. M. D. de Almeida, T. Footz, Anastassia Voronova
{"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}
ASN NEUROPub Date : 2022-01-01DOI: 10.1177/17590914221136365
María C Sanchez, Gustavo A Chiabrando
{"title":"Multitarget Activities of Müller Glial Cells and Low-Density Lipoprotein Receptor-Related Protein 1 in Proliferative Retinopathies.","authors":"María C Sanchez, Gustavo A Chiabrando","doi":"10.1177/17590914221136365","DOIUrl":"https://doi.org/10.1177/17590914221136365","url":null,"abstract":"<p><p>Müller glial cells (MGCs), the main glial component of the retina, play an active role in retinal homeostasis during development and pathological processes. They strongly monitor retinal environment and, in response to retinal imbalance, activate neuroprotective mechanisms mainly characterized by the increase of glial fibrillary acidic protein (GFAP). Under these circumstances, if homeostasis is not reestablished, the retina can be severely injured and GFAP contributes to neuronal degeneration, as they occur in several proliferative retinopathies such as diabetic retinopathy, sickle cell retinopathy and retinopathy of prematurity. In addition, MGCs have an active participation in inflammatory responses releasing proinflammatory mediators and metalloproteinases to the extracellular space and vitreous cavity. MGCs are also involved in the retinal neovascularization and matrix extracellular remodeling during the proliferative stage of retinopathies. Interestingly, low-density lipoprotein receptor-related protein 1 (LRP1) and its ligand α<sub>2</sub>-macroglobulin (α<sub>2</sub>M) are highly expressed in MGCs and they have been established to participate in multiple cellular and molecular activities with relevance in retinopathies. However, the exact mechanism of regulation of retinal LRP1 in MGCs is still unclear. Thus, the active participation of MGCs and LRP1 in these diseases, strongly supports the potential interest of them for the design of novel therapeutic approaches. In this review, we discuss the role of LRP1 in the multiple MGCs activities involved in the development and progression of proliferative retinopathies, identifying opportunities in the field that beg further research in this topic area.<b>Summary Statement</b>MGCs and LRP1 are active players in injured retinas, participating in key features such as gliosis and neurotoxicity, neovascularization, inflammation, and glucose control homeostasis during the progression of ischemic diseases, such as proliferative retinopathies.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221136365"},"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/02/61/10.1177_17590914221136365.PMC9629547.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659993","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}