ASN NEURO最新文献

{"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}

{"title":"Defibrinogenation Ameliorates Retinal Microgliosis and Inflammation in A CX3CR1-Independent Manner.","authors":"Borna Sarker, Sandra M Cardona, Kaira A Church, Difernando Vanegas, Priscila Velazquez, Colin Rorex, Derek Rodriguez, Andrew S Mendiola, Timothy S Kern, Nadia D Domingo, Robin Stephens, Isabel A Muzzio, Astrid E Cardona","doi":"10.1177/17590914221131446","DOIUrl":"10.1177/17590914221131446","url":null,"abstract":"<p><strong>Summary statement: </strong>Diabetic human and murine retinas revealed pronounced microglial morphological activation and vascular abnormalities associated with inflammation. Pharmacological fibrinogen depletion using ancrod dampened microglial morphology alterations, resolved fibrinogen accumulation, rescued axonal integrity, and reduced inflammation in the diabetic murine retina.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221131446"},"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/65/d0/10.1177_17590914221131446.PMC9557863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9109783","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":"Microglia at the Crossroads of Pathogen-Induced Neuroinflammation","authors":"A. M. Rodríguez, J. Rodríguez, G. Giambartolomei","doi":"10.1177/17590914221104566","DOIUrl":"https://doi.org/10.1177/17590914221104566","url":null,"abstract":"Microglia are the resident tissue macrophages of the central nervous system (CNS). Recent findings point out that in the steady state the major role of microglia, is to instruct and regulate the correct function of the neuronal networks and different components of the neurovascular unit in the adult CNS, while providing immune surveillance. Paradoxically, during CNS infection immune activation of microglia generates an inflammatory milieu that contributes to the clearance of the pathogen but can, in the process, harm nearby cells of CNS. Most of the knowledge about the harmful effects of activated microglia on CNS has arisen from studies on neurodegenerative diseases. In this review we will focus on the beneficial role and detrimental functions of microglial cells on the neighboring cells of the CNS upon infection.","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":"49394011","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":"Circadian Clock, Glucocorticoids and NF-κB Signaling in Neuroinflammation- Implicating Glucocorticoid Induced Leucine Zipper as a Molecular Link.","authors":"Mythily Srinivasan,&nbsp;Chandler Walker","doi":"10.1177/17590914221120190","DOIUrl":"https://doi.org/10.1177/17590914221120190","url":null,"abstract":"<p><p>Inflammation including neuroinflammation is considered a protective response and is directed to repair, regenerate, and restore damaged tissues in the central nervous system. Persistent inflammation due to chronic stress, age related accrual of free radicals, subclinical infections or other factors lead to reduced survival and increased neuronal death. Circadian abnormalities secondary to altered sleep/wake cycles is one of the earliest signs of neurodegenerative diseases. Brain specific or global deficiency of core circadian trans-activator brain and muscle ARNT (Arylhydrocarbon Receptor Nuclear Translocator)-like protein 1 (BMAL1) or that of the transrepressor REV-ERBα, impaired neural function and cognitive performance in rodents. Consistently, transcripts of inflammatory cytokines and host immune responses have been shown to exhibit diurnal variation, in parallel with the disruption of the circadian rhythm. Glucocorticoids that exhibit both a circadian rhythm similar to that of the core clock transactivator BMAL1 and tissue specific ultradian rhythm are critical in the control of neuroinflammation and re-establishment of homeostasis. It is widely accepted that the glucocorticoids suppress nuclear factor-kappa B (NF-κB) mediated transactivation and suppress inflammation. Recent mechanistic elucidations suggest that the core clock components also modulate NF-κB mediated transactivation in the brain and peripheral tissues. In this review we discuss evidence for interactions between the circadian clock components, glucocorticoids and NF-κB signaling responses in the brain and propose glucocorticoid induced leucine zipper (GILZ) encoded by Tsc22d3, as a molecular link that connect all three pathways in the maintenance of CNS homeostasis as well as in the pathogenesis of neuroinflammation-neurodegeneration.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221120190"},"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/0d/6a/10.1177_17590914221120190.PMC9629546.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40460474","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":"Neural Stem Cells in Adult Mammals are not Astrocytes.","authors":"Fernando Janczur Velloso, Sandhya Shankar, Vladimir Parpura, Pasko Rakic, Steven W Levison","doi":"10.1177/17590914221134739","DOIUrl":"10.1177/17590914221134739","url":null,"abstract":"<p><p>At the turn of the 21st century studies of the cells that resided in the adult mammalian subventricular zone (SVZ) characterized the neural stem cells (NSCs) as a subtype of astrocyte. Over the ensuing years, numerous studies have further characterized the properties of these NSCs and compared them to parenchymal astrocytes. Here we have evaluated the evidence collected to date to establish whether classifying the NSCs as astrocytes is appropriate and useful. We also performed a meta-analysis with 4 previously published datasets that used cell sorting and unbiased single-cell RNAseq to highlight the distinct gene expression profiles of adult murine NSCs and niche astrocytes. On the basis of our understanding of the properties and functions of astrocytes versus the properties and functions of NSCs, and from our comparative transcriptomic analyses we conclude that classifying the adult mammalian NSC as an astrocyte is potentially misleading. From our vantage point, it is more appropriate to refer to the cells in the adult mammalian SVZ that retain the capacity to produce new neurons and macroglia as NSCs without attaching the term \"astrocyte-like.\"</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221134739"},"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/ba/3b/10.1177_17590914221134739.PMC9638700.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9787401","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":"Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration.","authors":"Chen Liang,&nbsp;Damien Carrel,&nbsp;Nisha K Singh,&nbsp;Liam L Hiester,&nbsp;Isabelle Fanget,&nbsp;Hyuck Kim,&nbsp;Bonnie L Firestein","doi":"10.1177/17590914211062765","DOIUrl":"https://doi.org/10.1177/17590914211062765","url":null,"abstract":"<p><p>Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs. Thus, it is important to understand the regulation of PTMs during brain development as multiple developmental processes are dependent on MTs. In this study, we identified that carboxypeptidase E (CPE) changes tubulin polyglutamylation, a major PTM in the brain, and we examine the impact of CPE-mediated changes to polyglutamylation on cortical neuron migration and dendrite morphology. We show, for the first time, that overexpression of CPE increases the level of polyglutamylated α-tubulin while knockdown decreases the level of polyglutamylation. We also demonstrate that CPE-mediated changes to polyglutamylation are dependent on the CPE zinc-binding motif and that this motif is necessary for CPE action on p150^Glued localization. However, overexpression of a CPE mutant that does not increase MT glutamylation mimics the effects of overexpression of wild type CPE on dendrite branching. Furthermore, although overexpression of wild type CPE does not alter cortical neuron migration, overexpression of the mutant may act in a dominant-negative manner as it decreases the number of neurons that reach the cortical plate (CP), as we previously reported for CPE knockdown. Overall, our data suggest that CPE changes MT glutamylation and redistribution of p150^Glued and that this function of CPE is independent of its role in shaping dendrite development but plays a partial role in regulating cortical neuron migration.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914211062765"},"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/84/3e/10.1177_17590914211062765.PMC8755936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39809789","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":"Müller Cell Molecular Heterogeneity: Facts and Predictions","authors":"M. Lamas, Erick J. Martinez-Colin","doi":"10.1177/17590914221106903","DOIUrl":"https://doi.org/10.1177/17590914221106903","url":null,"abstract":"The retina was historically considered as an “approachable part of the brain”; advantageous, for its simplicity, to use as a model organ for deciphering cellular and molecular mechanisms underlying physiology and pathology of the nervous system. However, the most relevant discoveries arise precisely from unveiling the complexity of the retina. A complexity that partially relies on the layered organization of an extended variety of specialized neuronal and glial cellular types and subtypes. Based on functional, morphological or transcriptome data, over 40 subtypes of retinal ganglion cells or 60 subtypes of retinal amacrine cells have been described. A high degree of specialization, that may lead to segregation into functionally diverse subtypes, is also conceivable for Müller cells, a pleiotropic glial component of all vertebrate retinas. The essential role of Müller glia in retinal homeostasis maintenance involves participation in structural, metabolic and intercellular communication processes. Additionally, they are the only retinal cells that possess regenerative potential in response to injury or disease, and thus may be considered as therapeutic tools. In the assumption that functional heterogeneity might be driven by molecular heterogeneity this review aims to compile emerging evidence that could broaden our understanding of Müller cell biology and retinal physiology. Summary statement Müller glial cells exert multiple essential functions in retinal physiology and retinopathies reflecting perhaps the existence of distinct Müller cellular subpopulations. Harnessing Müller cell heterogeneity may serve to enhance new therapeutic approaches for retinal disease.","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":"43324845","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":"Astrocyte Cell Surface Antigen 2 and Other Potential Cell Surface Markers of Enteric glia in the Mouse Colon.","authors":"Vladimir Grubišić,&nbsp;Brian D Gulbransen","doi":"10.1177/17590914221083203","DOIUrl":"https://doi.org/10.1177/17590914221083203","url":null,"abstract":"<p><p>Enteric glia regulate gut functions in health and disease through diverse interactions with neurons and immune cells. Intracellular localization of traditional markers of enteric glia such as GFAP, s100b, and Sox10 makes them incompatible for studies that require antigen localization at the cell surface. Thus, new tools are needed for probing the heterogeneous roles of enteric glia at the protein, cell, and functional levels. Here we selected several cell surface antigens including Astrocyte Cell Surface Marker 2 (ACSA2), Cluster of differentiation 9 (CD9), lysophosphatidic acid receptor 1 (LPAR1), and Proteolipid protein 1 (PLP1) as potential markers of enteric glia. We tested their specificity for enteric glia using published single-cell/-nuclei and glia-specific translating mRNA enriched transcriptome datasets, immunolabeling, and flow cytometry. The data show that ACSA2 is a specific marker of mucosal and myenteric glia while other markers are suitable for identifying all subpopulations of enteric glia (LPAR1), glia and immune cells (CD9), or are not suitable for cell-surface labeling (PLP1). These new tools will be useful for future work focused on understanding specific glial functions in health and disease.<b>Summary Statement</b>This study identifies astrocyte cell surface antigen 2 as a novel marker of myenteric glia in the intestine. This, in combination with other markers identified in this study, could be used for selective targeting of enteric glia.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221083203"},"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/0f/23/10.1177_17590914221083203.PMC9125112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9302672","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":"Rab11 and Its Role in Neurodegenerative Diseases.","authors":"Pinky Sultana,&nbsp;Jiri Novotny","doi":"10.1177/17590914221142360","DOIUrl":"https://doi.org/10.1177/17590914221142360","url":null,"abstract":"<p><p>Vesicles mediate the trafficking of membranes/proteins in the endocytic and secretory pathways. These pathways are regulated by small GTPases of the Rab family. Rab proteins belong to the Ras superfamily of GTPases, which are significantly involved in various intracellular trafficking and signaling processes in the nervous system. Rab11 is known to play a key role especially in recycling many proteins, including receptors important for signal transduction and preservation of functional activities of nerve cells. Rab11 activity is controlled by GEFs (guanine exchange factors) and GAPs (GTPase activating proteins), which regulate its function through modulating GTP/GDP exchange and the intrinsic GTPase activity, respectively. Rab11 is involved in the transport of several growth factor molecules important for the development and repair of neurons. Overexpression of Rab11 has been shown to significantly enhance vesicle trafficking. On the other hand, a reduced expression of Rab11 was observed in several neurodegenerative diseases. Current evidence appears to support the notion that Rab11 and its cognate proteins may be potential targets for therapeutic intervention. In this review, we briefly discuss the function of Rab11 and its related interaction partners in intracellular pathways that may be involved in neurodegenerative processes.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"14 ","pages":"17590914221142360"},"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/6f/55/10.1177_17590914221142360.PMC9726856.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10342452","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":"Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper.","authors":"Megan L Morgan,&nbsp;Wulin Teo,&nbsp;Yda Hernandez,&nbsp;Craig Brideau,&nbsp;Karen Cummins,&nbsp;Hedwich F Kuipers,&nbsp;Peter K Stys","doi":"10.1177/17590914221126367","DOIUrl":"https://doi.org/10.1177/17590914221126367","url":null,"abstract":"<p><strong>Summary statement: </strong>The demyelinating effects of CPZ are not due to Cu deficiency but are instead consistent with acute toxicity of a CPZ + Cu complex.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":" ","pages":"17590914221126367"},"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/fa/74/10.1177_17590914221126367.PMC9483969.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40365159","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}