ASN NEURO最新文献

{"title":"Casein Kinase 2 Mediates HIV- and Opioid-Induced Pathologic Phosphorylation of TAR DNA Binding Protein 43 in the Basal Ganglia.","authors":"Michael Ohene-Nyako, Sara R Nass, Hope T Richard, Robert Lukande, Melanie R Nicol, MaryPeace McRae, Pamela E Knapp, Kurt F Hauser","doi":"10.1177/17590914231158218","DOIUrl":"10.1177/17590914231158218","url":null,"abstract":"<p><strong>Summary statement: </strong>HIV/HIV-1 Tat and morphine independently increase pathologic phosphorylation of TAR DNA binding protein 43 in the striatum. HIV- and opioid-induced pathologic phosphorylation of TAR DNA binding protein 43 may involve enhanced CK2 activity and protein levels.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231158218"},"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/06/3a/10.1177_17590914231158218.PMC9998424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868374","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":"Neuroprotection by Preconditioning in Mice is Dependent on MyD88-Mediated CXCL10 Expression in Endothelial Cells.","authors":"Zhihong Chen,&nbsp;Weiwei Hu,&nbsp;Mynor J Mendez,&nbsp;Zachary C Gossman,&nbsp;Anthony Chomyk,&nbsp;Brendan T Boylan,&nbsp;Grahame J Kidd,&nbsp;Timothy W Phares,&nbsp;Cornelia C Bergmann,&nbsp;Bruce D Trapp","doi":"10.1177/17590914221146365","DOIUrl":"10.1177/17590914221146365","url":null,"abstract":"<p><p>The central nervous system (CNS) can be preconditioned to resist damage by peripheral pretreatment with low-dose gram-negative bacterial endotoxin lipopolysaccharide (LPS). Underlying mechanisms associated with transient protection of the cerebral cortex against traumatic brain injury include increased neuronal production of antiapoptotic and neurotrophic molecules, microglial-mediated displacement of inhibitory presynaptic terminals innervating the soma of cortical projection neurons, and synchronized firing of cortical projection neurons. However, the cell types and signaling responsible for these neuronal and microglial changes are unknown. A fundamental question is whether LPS penetrates the CNS or acts on the luminal surface of brain endothelial cells, thereby triggering an indirect parenchymal neuroprotective response. The present study shows that a low-dose intraperitoneal LPS treatment increases brain endothelial cell activation markers CD54, but does not open the blood-brain barrier or alter brain endothelial cell tight junctions as assessed by electron microscopy. NanoString nCounter transcript analyses of CD31-positive brain endothelial cells further revealed significant upregulation of <i>Cxcl10, C3, Ccl2, Il1β, Cxcl2,</i> and <i>Cxcl1</i>, consistent with identification of myeloid differentiation primary response 88 (MyD88) as a regulator of these transcripts by pathway analysis. Conditional genetic endothelial cell gene ablation approaches demonstrated that both MyD88-dependent Toll-like receptor 4 (TLR4) signaling and <i>Cxcl10</i> expression are essential for LPS-induced neuroprotection and microglial activation. These results suggest that C-X-C motif chemokine ligand 10 (CXCL10) production by endothelial cells in response to circulating TLR ligands may directly or indirectly signal to CXCR3 on neurons and/or microglia. Targeted activation of brain endothelial receptors may thus provide an attractive approach for inducing transient neuroprotection.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914221146365"},"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/3b/50/10.1177_17590914221146365.PMC9810995.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211960","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":"Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice.","authors":"Takuya Kawamura, Gagandeep Singh Mallah, Maryam Ardalan, Tetyana Chumak, Pernilla Svedin, Lina Jonsson, Seyedeh Marziyeh Jabbari Shiadeh, Fanny Goretta, Tomoaki Ikeda, Henrik Hagberg, Mats Sandberg, Carina Mallard","doi":"10.1177/17590914231198983","DOIUrl":"10.1177/17590914231198983","url":null,"abstract":"<p><strong>Summary statement: </strong>Neonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD⁺) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD⁺ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231198983"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105321","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":"Transferrin Enhances Neuronal Differentiation.","authors":"María Julia Pérez,&nbsp;Tomas Roberto Carden,&nbsp;Paula Ayelen Dos Santos Claro,&nbsp;Susana Silberstein,&nbsp;Pablo Martin Páez,&nbsp;Veronica Teresita Cheli,&nbsp;Jorge Correale,&nbsp;Juana M Pasquini","doi":"10.1177/17590914231170703","DOIUrl":"https://doi.org/10.1177/17590914231170703","url":null,"abstract":"<p><p>Although transferrin (Tf) is a glycoprotein best known for its role in iron delivery, iron-independent functions have also been reported. Here, we assessed apoTf (aTf) treatment effects on Neuro-2a (N2a) cells, a mouse neuroblastoma cell line which, once differentiated, shares many properties with neurons, including process outgrowth, expression of selective neuronal markers, and electrical activity. We first examined the binding of Tf to its receptor (TfR) in our model and verified that, like neurons, N2a cells can internalize Tf from the culture medium. Next, studies on neuronal developmental parameters showed that Tf increases N2a survival through a decrease in apoptosis. Additionally, Tf accelerated the morphological development of N2a cells by promoting neurite outgrowth. These pro-differentiating effects were also observed in primary cultures of mouse cortical neurons treated with aTf, as neurons matured at a higher rate than controls and showed a decrease in the expression of early neuronal markers. Further experiments in iron-enriched and iron-deficient media showed that Tf preserved its pro-differentiation properties in N2a cells, with results hinting at a modulatory role for iron. Moreover, N2a-microglia co-cultures revealed an increase in IL-10 upon aTf treatment, which may be thought to favor N2a differentiation. Taken together, these findings suggest that Tf reduces cell death and favors the neuronal differentiation process, thus making Tf a promising candidate to be used in regenerative strategies for neurodegenerative diseases.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231170703"},"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/cc/6f/10.1177_17590914231170703.PMC10134178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507415","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":"Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline.","authors":"G C Nascimento,&nbsp;M Bortolanza,&nbsp;A Bribian,&nbsp;G C Leal-Luiz,&nbsp;R Raisman-Vozari,&nbsp;L López-Mascaraque,&nbsp;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}

{"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}

{"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":"Acute Manganese Exposure Modifies the Translation Machinery <i>via</i> PI3K/Akt Signaling in Glial Cells.","authors":"Jzmín Soto-Verdugo,&nbsp;Janisse Siva-Parra,&nbsp;Luisa C Hernández-Kelly,&nbsp;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}

{"title":"Dendritic Polyglycerol Amine: An Enhanced Substrate to Support Long-Term Neural Cell Culture.","authors":"Jean-Pierre Clément,&nbsp;Laila Al-Alwan,&nbsp;Stephen D Glasgow,&nbsp;Avya Stolow,&nbsp;Yi Ding,&nbsp;Thaiany Quevedo Melo,&nbsp;Anouar Khayachi,&nbsp;Yumin Liu,&nbsp;Markus Hellmund,&nbsp;Rainer Haag,&nbsp;Austen J Milnerwood,&nbsp;Peter Grütter,&nbsp;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}

{"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}