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Hilton Foundation","doi-asserted-by":"publisher","award":["20130231"],"award-info":[{"award-number":["20130231"]}],"id":[{"id":"10.13039\/100000910","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000910","name":"Conrad N. Hilton Foundation","doi-asserted-by":"publisher","award":["20150232"],"award-info":[{"award-number":["20150232"]}],"id":[{"id":"10.13039\/100000910","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tom Sherak MS Hope Foundation, the Rhoda Goetz Foundation for MS, the Jewish Community Foundation and the Dunk MS Foundation."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple sclerosis (MS) is a neuroinflammatory multifocal disorder. Optic neuritis is common in MS and leads to visual disability. No current treatments repair this damage. Discerning gene expression changes within specific cell types in optic nerve (ON) may suggest new treatment targets for visual disability in MS. Astrocytes are pivotal regulators of neuroinflammation, playing either detrimental or beneficial roles. Here, we used RiboTag technology to characterize the astrocyte-specific transcriptome in ON in the experimental autoimmune encephalomyelitis (EAE) model of MS. RNA sequencing analysis showed the Complement Cascade and Cholesterol Biosynthesis Pathways as the most enriched and de-enriched pathways, respectively, in ON astrocytes in EAE. Expression of complement component 3 (C3) was confirmed to be increased in ON astrocytes at the protein level during EAE. A bigger increase in C3 expressing ON astrocytes was found in EAE females versus healthy females, as compared to that in EAE males versus healthy males. Also, there was worse retinal ganglion cell (RGC) and axonal loss in EAE females. Regression analyses showed a negative correlation between C3 expressing astrocytes and RGC density. This cell-specific and sex-specific investigation of the optic nerve provides targets for the development of therapeutic strategies tailored for optic neuritis in MS.<\/jats:p>","DOI":"10.1038\/s41598-019-46232-6","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T10:03:11Z","timestamp":1562752991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["The astrocyte transcriptome in EAE optic neuritis shows complement activation and reveals a sex difference in astrocytic C3 expression"],"prefix":"10.1038","volume":"9","author":[{"given":"Alessia","family":"Tassoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vista","family":"Farkhondeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Sofroniew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda R.","family":"Voskuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"46232_CR1","doi-asserted-by":"publisher","first-page":"E302","DOI":"10.1073\/pnas.1716032115","volume":"115","author":"N Itoh","year":"2018","unstructured":"Itoh, N. et al. Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes. Proc Natl Acad Sci USA 115, E302\u2013E309, https:\/\/doi.org\/10.1073\/pnas.1716032115 (2018).","journal-title":"Proc Natl Acad Sci USA"},{"key":"46232_CR2","doi-asserted-by":"publisher","first-page":"13939","DOI":"10.1073\/pnas.0907143106","volume":"106","author":"E Sanz","year":"2009","unstructured":"Sanz, E. et al. Cell-type-specific isolation of ribosome-associated mRNA from complex tissues. Proc Natl Acad Sci USA 106, 13939\u201313944, https:\/\/doi.org\/10.1073\/pnas.0907143106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"46232_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nature17623","volume":"532","author":"MA Anderson","year":"2016","unstructured":"Anderson, M. A. et al. Astrocyte scar formation aids central nervous system axon regeneration. 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