{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:07:48Z","timestamp":1790723268172,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KI 1469\/8-1; MK"],"award-info":[{"award-number":["KI 1469\/8-1; MK"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Microglia play an important role in the pathology of various central nervous system disorders, including multiple sclerosis (MS). While different methods exist to evaluate the extent of microglia activation, comparative studies investigating the sensitivity of these methods are missing for most models. In this study, we systematically evaluated which of the three commonly used histological methods (id est, quantification of microglia density, densitometrically evaluated staining intensity, or cellular morphology based on the determination of a ramification index, all measured in anti-ionized calcium-binding adaptor protein-1 (IBA1) immunohistochemical stains) is the most sensitive method to detect subtle changes in the microglia activation status in the context of MS. To this end, we used the toxin-induced cuprizone model which allows the experimental induction of a highly reproducible demyelination in several central nervous system regions, paralleled by early microglia activation. In this study, we showed that after 3 weeks of cuprizone intoxication, all methods reveal a significant microglia activation in the white matter corpus callosum. In contrast, in the affected neocortical grey matter, the evaluation of anti-IBA1 cell morphologies was the most sensitive method to detect subtle changes of microglial activation. The results of this study provide a useful guide for future immunohistochemical evaluations in the cuprizone and other neurodegenerative models.<\/jats:p>","DOI":"10.3390\/cells11111723","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T22:04:06Z","timestamp":1653429846000},"page":"1723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariela","family":"Wittekindt","sequence":"first","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-7344","authenticated-orcid":false,"given":"Hannes","family":"Kaddatz","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-8904","authenticated-orcid":false,"given":"Sarah","family":"Joost","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Staffeld","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamen","family":"Bitar","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-9052","authenticated-orcid":false,"given":"Markus","family":"Kipp","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Frintrop","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1194637","article-title":"Fate mapping analysis reveals that adult microglia derive from primitive macrophages","volume":"330","author":"Ginhoux","year":"2010","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.3389\/fimmu.2018.01014","article-title":"Microglial Dynamics During Human Brain Development","volume":"9","author":"Menassa","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/nn.4325","article-title":"Age-related myelin degradation burdens the clearance function of microglia during aging","volume":"19","author":"Safaiyan","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1523\/JNEUROSCI.4363-08.2009","article-title":"Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals","volume":"29","author":"Wake","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Akiyoshi, R., Wake, H., Kato, D., Horiuchi, H., Ono, R., Ikegami, A., Haruwaka, K., Omori, T., Tachibana, Y., and Moorhouse, A.J. (2018). Microglia Enhance Synapse Activity to Promote Local Network Synchronization. eNeuro, 5.","DOI":"10.1523\/ENEURO.0088-18.2018"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-981-13-9913-8_13","article-title":"Microglia in Parkinson\u2019s Disease","volume":"1175","author":"Ho","year":"2019","journal-title":"Adv Exp. Med. Biol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3389\/fimmu.2020.00374","article-title":"Microglia in Multiple Sclerosis: Friend or Foe?","volume":"11","author":"Guerrero","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00401-014-1310-2","article-title":"Macrophage subsets and microglia in multiple sclerosis","volume":"128","author":"Bogie","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/glia.23726","article-title":"Pathology of inflammatory diseases of the nervous system: Human disease versus animal models","volume":"68","author":"Lassmann","year":"2020","journal-title":"Glia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jneuroim.2010.09.020","article-title":"Inflammation and gliosis in neurological diseases\u2014Clinical implications","volume":"231","author":"Czlonkowska","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3389\/fncel.2018.00488","article-title":"Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response","volume":"12","author":"Bachiller","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fncel.2018.00215","article-title":"Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNgamma+TNFalpha) and Reprogramming by Resolving Cytokines (IL-4, IL-10)","volume":"12","author":"Lively","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41583-018-0053-9","article-title":"Multiple sclerosis and cognition: Synaptic failure and network dysfunction","volume":"19","author":"Portaccio","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00011-011-0339-0","article-title":"The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis","volume":"60","author":"Kipp","year":"2011","journal-title":"Inflamm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41582-019-0253-6","article-title":"When encephalitogenic T cells collaborate with microglia in multiple sclerosis","volume":"15","author":"Dong","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","unstructured":"International Multiple Sclerosis Genetics Consortium (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science, 365, eaav7188."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41582-019-0184-2","article-title":"The pro-remyelination properties of microglia in the central nervous system","volume":"15","author":"Lloyd","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00401-020-02193-z","article-title":"TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis","volume":"140","author":"Cignarella","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41593-020-00757-6","article-title":"Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis","volume":"24","author":"Berghoff","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neuroscience.2018.02.028","article-title":"Stereological Analysis of Microglia in Aged Male and Female Fischer 344 Rats in Socially Relevant Brain Regions","volume":"377","author":"Perkins","year":"2018","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/jnr.21946","article-title":"Cuprizone treatment induces demyelination and astrocytosis in the mouse hippocampus","volume":"87","author":"Norkute","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0165-5728(98)00168-4","article-title":"Microglial\/macrophage accumulation during cuprizone-induced demyelination in C57BL\/6 mice","volume":"92","author":"Hiremath","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"ref_25","first-page":"103","article-title":"Multiple Morphometric Assessment of Microglial Cells in Deafferented Spinal Trigeminal Nucleus","volume":"13","author":"Martin","year":"2019","journal-title":"Front. Neuroanat."},{"key":"ref_26","first-page":"4240","article-title":"Effect of Intrastriatal 6-OHDA Lesions on Extrastriatal Brain Structures in the Mouse","volume":"55","author":"Becker","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4103\/2347-8659.139719","article-title":"A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining: Cell body to cell size ratio","volume":"1","author":"Hovens","year":"2014","journal-title":"Neuroimmunol. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/s41598-017-01747-8","article-title":"Characterizing microglia activation: A spatial statistics approach to maximize information extraction","volume":"7","author":"Davis","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12031-015-0595-5","article-title":"Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice","volume":"57","author":"Goldberg","year":"2015","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fnagi.2018.00278","article-title":"Age Influences Microglial Activation After Cuprizone-Induced Demyelination","volume":"10","author":"Klein","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s12031-017-0903-3","article-title":"Cuprizone-Containing Pellets Are Less Potent to Induce Consistent Demyelination in the Corpus Callosum of C57BL\/6 Mice","volume":"61","author":"Hochstrasser","year":"2017","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/bph.12938","article-title":"The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination","volume":"172","author":"Slowik","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/glia.23937","article-title":"Cuprizone-induced demyelination triggers a CD8-pronounced T cell recruitment","volume":"69","author":"Kaddatz","year":"2021","journal-title":"Glia"},{"key":"ref_34","unstructured":"Paxinos, G., and Franklin, K.B.J. (2004). The Mouse Brain in Stereotaxic Coordinates, Elsevier Academic Press. [2nd ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00418-019-01786-4","article-title":"Continuous cuprizone intoxication allows active experimental autoimmune encephalomyelitis induction in C57BL\/6 mice","volume":"152","author":"Yakimov","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhan, J., Yakimov, V., Ruhling, S., Fischbach, F., Nikolova, E., Joost, S., Kaddatz, H., Greiner, T., Frenz, J., and Holzmann, C. (2019). High Speed Ventral Plane Videography as a Convenient Tool to Quantify Motor Deficits during Pre-Clinical Experimental Autoimmune Encephalomyelitis. Cells, 8.","DOI":"10.3390\/cells8111439"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1007\/s12031-021-01800-2","article-title":"Long-Term Glucose Starvation Induces Inflammatory Responses and Phenotype Switch in Primary Cortical Rat Astrocytes","volume":"71","author":"Kogel","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/glia.22367","article-title":"Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions","volume":"60","author":"Clarner","year":"2012","journal-title":"Glia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/1097-4547(20000801)61:3<251::AID-JNR3>3.0.CO;2-W","article-title":"Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination\/remyelination","volume":"61","author":"Mason","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s10571-013-9975-y","article-title":"Short-term cuprizone feeding induces selective amino acid deprivation with concomitant activation of an integrated stress response in oligodendrocytes","volume":"33","author":"Goldberg","year":"2013","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12031-012-9773-x","article-title":"Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination","volume":"48","author":"Buschmann","year":"2012","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/glia.20297","article-title":"Upregulation of the stress-associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues","volume":"53","author":"Plant","year":"2006","journal-title":"Glia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.nbd.2013.10.023","article-title":"Galectin-3 controls the response of microglial cells to limit cuprizone-induced demyelination","volume":"62","author":"Hoyos","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.4049\/jimmunol.1401459","article-title":"CXCL10 triggers early microglial activation in the cuprizone model","volume":"194","author":"Clarner","year":"2015","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/glia.23605","article-title":"Glial fibrillary acidic protein expression alters astrocytic chemokine release and protects mice from cuprizone-induced demyelination","volume":"67","author":"Kramann","year":"2019","journal-title":"Glia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1742-2094-11-109","article-title":"CXCR3 modulates glial accumulation and activation in cuprizone-induced demyelination of the central nervous system","volume":"11","author":"Krauthausen","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/brain\/aws262","article-title":"Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination","volume":"136","author":"Skripuletz","year":"2013","journal-title":"Brain J. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/glia.24164","article-title":"Transmembrane protein 119 is neither a specific nor a reliable marker for microglia","volume":"70","author":"Vankriekelsvenne","year":"2022","journal-title":"Glia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/brain\/awx113","article-title":"Loss of \u2018homeostatic\u2019 microglia and patterns of their activation in active multiple sclerosis","volume":"140","author":"Zrzavy","year":"2017","journal-title":"Brain J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/glia.23980","article-title":"Activated microglia drive demyelination via CSF1R signaling","volume":"69","author":"Marzan","year":"2021","journal-title":"Glia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0022-510X(87)90218-8","article-title":"Microglia are the major cell type expressing MHC class II in human white matter","volume":"80","author":"Hayes","year":"1987","journal-title":"J. Neurol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/eji.201847540","article-title":"Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination","volume":"48","author":"Wolf","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ana.21719","article-title":"Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"66","author":"Vogt","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s12031-016-0858-9","article-title":"Design-Based Stereology for Evaluation of Histological Parameters","volume":"61","author":"Kipp","year":"2017","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_56","first-page":"57","article-title":"Medroxyprogesterone acetate attenuates demyelination, modulating microglia activation, in a cuprizone neurotoxic demyelinating mouse model","volume":"10","author":"Mohammadi","year":"2021","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/glia.23540","article-title":"Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination","volume":"67","author":"Pasquini","year":"2019","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12974-020-01911-4","article-title":"T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an \u03b1-synuclein rat model of Parkinson\u2019s disease","volume":"17","author":"Subbarayan","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1006\/bbrc.2001.5388","article-title":"Iba1 is an actin-cross-linking protein in macrophages\/microglia","volume":"286","author":"Sasaki","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fncel.2020.00284","article-title":"Beneficial Roles of Microglia and Growth Factors in MS, a Brief Review","volume":"14","author":"Pons","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"222","DOI":"10.4103\/1673-5374.226386","article-title":"Microglial dynamics during brain development","volume":"13","author":"Okajima","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fncel.2013.00003","article-title":"Quantitating the subtleties of microglial morphology with fractal analysis","volume":"7","author":"Karperien","year":"2013","journal-title":"Front. Cell Neurosci."},{"key":"ref_63","first-page":"e57648","article-title":"Quantifying Microglia Morphology from Photomicrographs of Immunohistochemistry Prepared Tissue Using ImageJ","volume":"136","author":"Young","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-2094-10-4","article-title":"A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion","volume":"10","author":"Morrison","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1093\/cercor\/bhs151","article-title":"Chronic stress induced remodeling of the prefrontal cortex: Structural re-organization of microglia and the inhibitory effect of minocycline","volume":"23","author":"Hinwood","year":"2013","journal-title":"Cereb. Cortex"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105449","DOI":"10.1016\/j.nbd.2021.105449","article-title":"Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination","volume":"157","author":"Roufagalas","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.nbd.2011.09.003","article-title":"Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease","volume":"45","author":"Franciosi","year":"2012","journal-title":"Neurobiol. Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/11\/1723\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:17:26Z","timestamp":1760138246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/11\/1723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":67,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["cells11111723"],"URL":"https:\/\/doi.org\/10.3390\/cells11111723","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]}}}