{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:57:50Z","timestamp":1760147870794,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"National Institute of Health NINDS","doi-asserted-by":"publisher","award":["NS197387","NS109077"],"award-info":[{"award-number":["NS197387","NS109077"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroglia"],"abstract":"<jats:p>Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by the early and prominent pathology of the cerebellar Purkinje cells that results in balance and coordination deficits. We previously demonstrated that cerebellar astrocytes contribute to SCA1 pathogenesis in a biphasic, stage of disease-dependent manner. We found that pro-inflammatory transcriptional regulator nuclear factor \u03ba-light-chain-enhancer of activated B cells (NF-\u03baB) signaling in astrocytes has a neuroprotective role during early-stage SCA1. Here, we sought to examine whether further inducing NF-\u03baB activation in astrocytes of SCA1 model mice at an early stage of the disease has therapeutic benefits. To perform this task, we created a novel Slc1a3-CreERT\/IKK\u03b2CA\/ATXN1[82Q] triple transgenic mouse model in which TMX injection at 4 weeks of age results in the expression of constitutively active inhibitor of kB kinase beta (IKK\u03b2CA), the main activator of NF-\u03baB signaling. As we evaluated SCA1-like phenotypes, we noticed that ATXN1[82Q] mice did not exhibit motor deficits anymore, even at very late stages of the disease. We sequenced the mutant ATXN1 gene and discovered that the CAG repeat number had decreased from 82 to 71. However, despite the loss of motor phenotype, other well-characterized SCA1-changes, including atrophy of Purkinje cell dendrites, hallmarks of cerebellar astrogliosis and microgliosis, and Purkinje cell disease-associated gene expression changes, were still detectable in ATXN1[71Q] mice. We found delayed PC atrophy and calbindin reduction in SCA1 mice expressing IKK\u03b2CA in astrocytes implicating beneficial effects of increased NF-\u03baB signaling on Purkinje cell pathology. The change in the motor phenotype of SCA1 mice with CAG reduction prevented us from evaluating the neuroprotective potential of IKK\u03b2CA on motor deficits in these mice.<\/jats:p>","DOI":"10.3390\/neuroglia4010005","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T03:59:32Z","timestamp":1678247972000},"page":"52-68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modest Reduction in CAG Repeat Length Rescues Motor Deficits but Not Purkinje Cell Pathology and Gliosis in Spinocerebellar Ataxia Type 1 Mice"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8952-6417","authenticated-orcid":false,"given":"Stephen","family":"Gilliat","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-8313","authenticated-orcid":false,"given":"Juao-Guilherme","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genevieve","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaelin","family":"Sbrocco","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wensheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Cvetanovic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7425","DOI":"10.1074\/jbc.R800041200","article-title":"Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, Spinocerebellar ataxia type 1","volume":"284","author":"Zoghbi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng0894-513","article-title":"Identification and characterization of the gene causing type 1 spinocerebellar ataxia","volume":"7","author":"Banfi","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng0793-221","article-title":"Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1","volume":"4","author":"Orr","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12311-008-0009-0","article-title":"Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1","volume":"7","author":"Goold","year":"2008","journal-title":"Cerebellum"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/ana.410230609","article-title":"Spinocerebellar Ataxia: Variable Age of Onset and Linkage to Human Leukocyte Antigen in a Large Kindred","volume":"23","author":"Zoghbi","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrn.2017.92","article-title":"Polyglutamine spinocerebellar ataxias\u2014From genes to potential treatments","volume":"18","author":"Paulson","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1007\/s00415-020-09815-2","article-title":"Natural history of most common spinocerebellar ataxia: A systematic review and meta-analysis","volume":"268","author":"Diallo","year":"2021","journal-title":"J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1212\/WNL.0b013e31822e7ca0","article-title":"The natural history of spinocerebellar","volume":"3974","author":"Jacobi","year":"2011","journal-title":"Neurology"},{"key":"ref_9","unstructured":"Donato, S.D., Mariotti, C., and Taroni, F. (2012). Handbook of Clinical Neurology, Elsevier. [1st ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1212\/WNL.45.1.24","article-title":"Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms","volume":"45","author":"Genis","year":"1995","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S1474-4422(18)30042-5","article-title":"Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): A longitudinal cohort study","volume":"17","author":"Diallo","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/S1474-4422(15)00202-1","article-title":"Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study","volume":"14","author":"Jacobi","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/j.1365-2990.2012.01259.x","article-title":"Spinocerebellar ataxia type 1 (SCA1): New pathoanatomical and clinico-pathological insights","volume":"38","author":"Timmann","year":"2012","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-012-1000-x","article-title":"Brain pathology of spinocerebellar ataxias","volume":"124","author":"Seidel","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/ng0595-94","article-title":"Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals","volume":"10","author":"Servadio","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cerrato, V. (2020). Cerebellar astrocytes: Much more than passive bystanders in ataxia pathophysiology. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030757"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1046\/j.0022-7722.2002.00021.x","article-title":"Cytodifferentiation of Bergmann glia and its relationship with Purkinje cells","volume":"77","author":"Yamada","year":"2002","journal-title":"Anat. Sci. Int.\/Jpn. Assoc. Anat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1073\/pnas.1120380109","article-title":"Bergmann glia modulate cerebellar Purkinje cell bistability via Ca2+\u2212dependent K+ uptake","volume":"109","author":"Wang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.neuron.2013.12.034","article-title":"Reactive gliosis and the multicellular response to CNS damage and disease","volume":"81","author":"Burda","year":"2014","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neulet.2013.12.071","article-title":"The dual role of astrocyte activation and reactive gliosis","volume":"565","author":"Pekny","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: Biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"a020628","DOI":"10.1101\/cshperspect.a020628","article-title":"Astrocytes in Neurodegenerative Disease","volume":"7","author":"Phatnani","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.neuron.2008.10.013","article-title":"The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease","volume":"60","author":"Barres","year":"2008","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.200908164","article-title":"Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond","volume":"187","author":"Ilieva","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/nn1988","article-title":"Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease","volume":"10","author":"Lobsiger","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1523\/JNEUROSCI.3693-15.2016","article-title":"Khakh Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington\u2019s Disease Model Mice","volume":"36","author":"Jiang","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sheeler, C., Rosa, J., Ferro, A., Mcadams, B., Borgenheimer, E., and Cvetanovic, M. (2020). Glia in Neurodegeneration: The Housekeeper, the Defender and the Perpetrator. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239188"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nn2047","article-title":"Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis","volume":"11","author":"Yamanaka","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neuroscience.2015.01.003","article-title":"Early activation of microglia and astrocytes in mouse models of spinocerebellar ataxia type 1","volume":"289","author":"Cvetanovic","year":"2015","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ferro, A., Qu, W., Lukowicz, A., Svedberg, D., Johnson, A., and Cvetanovic, M. (2018). Inhibition of NF-\u03baB signaling in IKK\u03b2 F\/F;LysM Cre mice causes motor deficits but does not alter pathogenesis of Spinocerebellar ataxia type 1. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200013"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/0092-8674(95)90273-2","article-title":"SCA1 transgenic mice: A model for neurodegeneration caused by an expanded CAG trinucleotide repeat","volume":"82","author":"Burright","year":"1995","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/glia.23451","article-title":"Astroglia contribute to the pathogenesis of spinocerebellar ataxia Type 1 ( SCA1 ) in a biphasic, stage-of-disease specific manner","volume":"66","author":"Kim","year":"2018","journal-title":"Glia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Choi, S.S., Lee, H.J., Lim, I., Satoh, J., and Kim, S.U. (2014). Human Astrocytes: Secretome Profiles of Cytokines and Chemokines. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092325"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1093\/hmg\/ddt036","article-title":"A critical role of astrocyte-mediated nuclear factor-\u03baB-dependent inflammation in huntington\u2019s disease","volume":"22","author":"Hsiao","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","first-page":"175","article-title":"NF- B Signaling Pathways: Role in Nervous System Physiology and Pathology","volume":"19","author":"Soler","year":"2012","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.284.5412.309","article-title":"Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation","volume":"284","author":"Delhase","year":"1999","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/glia.10010","article-title":"Activation of astrocyte intracellular signaling pathways by interleukin-1 in rat primary striatal cultures","volume":"37","author":"Dunn","year":"2002","journal-title":"Glia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0092-8674(00)80406-7","article-title":"The IkB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKa and IKKb, Necessary for IkB Phosphorylation and NF-kB Activation","volume":"91","author":"Zandi","year":"1997","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ni.2065","article-title":"Crosstalk in NF-\u03baB signaling pathways","volume":"12","author":"Oeckinghaus","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S1097-2765(02)00477-X","article-title":"The phosphorylation status of nuclear NF-kB determines its association with CBP\/p300 or HDAC-1","volume":"9","author":"Zhong","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1084\/jem.20041918","article-title":"Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury","volume":"202","author":"Brambilla","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.4049\/jimmunol.0802954","article-title":"Transgenic Inhibition of Astroglial NF-\u03baB Improves Functional Outcome in Experimental Autoimmune Encephalomyelitis by Suppressing Chronic Central Nervous System Inflammation","volume":"182","author":"Brambilla","year":"2009","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.pain.2010.01.001","article-title":"Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury","volume":"148","author":"Fu","year":"2010","journal-title":"Pain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1523\/JNEUROSCI.2117-15.2016","article-title":"Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer\u2019s Disease","volume":"36","author":"Lian","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.immuni.2006.04.005","article-title":"Canonical NF-??B Activity, Dispensable for B Cell Development, Replaces BAFF-Receptor Signals and Promotes B Cell Proliferation upon Activation","volume":"24","author":"Sasaki","year":"2006","journal-title":"Immunity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5806","DOI":"10.1523\/JNEUROSCI.6311-11.2013","article-title":"Purkinje Cell Ataxin-1 Modulates Climbing Fiber Synaptic Input in Developing and Adult Mouse Cerebellum","volume":"33","author":"Ebner","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12974-017-0880-z","article-title":"Inhibition of colony-stimulating factor 1 receptor early in disease ameliorates motor deficits in SCA1 mice","volume":"14","author":"Qu","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1523\/JNEUROSCI.17-19-07385.1997","article-title":"Purkinje Cell Expression of a Mutant Allele of SCA1 in Transgenic Mice Leads to Disparate Effects on Motor Behaviors, Followed by a Progressive Cerebellar Dysfunction and Histological Alterations","volume":"17","author":"Clark","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.cell.2006.09.036","article-title":"ROR a-Mediated Purkinje Cell Development Determines Disease Severity in Adult SCA1 Mice","volume":"127","author":"Serra","year":"2006","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/nm1076","article-title":"RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia","volume":"10","author":"Xia","year":"2004","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.neuron.2010.08.022","article-title":"SCA1-like disease in mice expressing wild-type Ataxin-1 with a serine to aspartic acid replacement at residue 776","volume":"67","author":"Duvick","year":"2010","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0092-8674(00)81781-X","article-title":"Ataxin-1 Nuclear Localization and Aggregation: Role in Polyglutamine-Induced Disease in SCA1 Transgenic Mice","volume":"95","author":"Klement","year":"1998","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6444","DOI":"10.1523\/JNEUROSCI.1156-20.2020","article-title":"NF-kB activation accounts for the cytoprotective effects of PERK activation on oligodendrocytes during EAE","volume":"40","author":"Lei","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.neuron.2015.02.022","article-title":"Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance","volume":"85","author":"Madisen","year":"2015","journal-title":"Neuron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.neuron.2014.04.038","article-title":"Norepinephrine controls astroglial responsiveness to local circuit activity","volume":"82","author":"Paukert","year":"2014","journal-title":"Neuron"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.cell.2015.02.012","article-title":"Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels","volume":"160","author":"Gennarino","year":"2015","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3389\/fncel.2018.00509","article-title":"Brain Derived Neurotrophic Factor ( BDNF ) Delays Onset of Pathogenesis in Transgenic Mouse Model of Spinocerebellar Ataxia Type 1 (SCA1)","volume":"12","author":"Mellesmoen","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.1227901","article-title":"Microglia: Scapegoat, saboteur, or something else?","volume":"339","author":"Aguzzi","year":"2013","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/glia.21104","article-title":"Microglia in the CNS: Immigrants from another world","volume":"59","author":"Prinz","year":"2011","journal-title":"Glia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/glia.22738","article-title":"Microglial regulation of immunological and neuroprotective functions of astroglia","volume":"63","author":"Chen","year":"2015","journal-title":"Glia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuron.2014.11.018","article-title":"NF\u03baB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer\u2019s Disease","volume":"85","author":"Lian","year":"2015","journal-title":"Neuron"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-017-0157-0","article-title":"Transient IKK2 activation in astrocytes initiates selective non-cell-autonomous neurodegeneration","volume":"12","author":"Lattke","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e98697","DOI":"10.15252\/embj.201798697","article-title":"NF-\u03baB activation in astrocytes drives a stage-specific beneficial neuroimmunological response in ALS","volume":"37","author":"Schurr","year":"2018","journal-title":"EMBO J."}],"container-title":["Neuroglia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-6980\/4\/1\/5\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:50:21Z","timestamp":1760122221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-6980\/4\/1\/5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["neuroglia4010005"],"URL":"https:\/\/doi.org\/10.3390\/neuroglia4010005","relation":{},"ISSN":["2571-6980"],"issn-type":[{"type":"electronic","value":"2571-6980"}],"subject":[],"published":{"date-parts":[[2023,3,7]]}}}