Show simple item record

dc.contributor.authorO'Shea, RD
dc.contributor.authorLau, CL
dc.contributor.authorZulaziz, N
dc.contributor.authorMaclean, FL
dc.contributor.authorNisbet, DR
dc.contributor.authorHome, MK
dc.contributor.authorBeart, PM
dc.date.accessioned2021-02-05T00:23:08Z
dc.date.available2021-02-05T00:23:08Z
dc.date.issued2015-02-20
dc.identifier.citationO'Shea, R. D., Lau, C. L., Zulaziz, N., Maclean, F. L., Nisbet, D. R., Home, M. K. & Beart, P. M. (2015). Transcriptomic analysis and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis. FRONTIERS IN NEUROSCIENCE, 9 (FEB), https://doi.org/10.3389/fnins.2015.00050.
dc.identifier.issn1662-4548
dc.identifier.urihttp://hdl.handle.net/11343/259983
dc.description.abstractAstrocytes provide trophic, structural and metabolic support to neurons, and are considered genuine targets in regenerative neurobiology, as their phenotype arbitrates brain integrity during injury. Inhibitors of Rho kinase (ROCK) cause stellation of cultured 2D astrocytes, increased L-glutamate transport, augmented G-actin, and elevated expression of BDNF and anti-oxidant genes. Here we further explored the signposts of a cytotrophic, "healthy" phenotype by data-mining of our astrocytic transcriptome in the presence of Fasudil. Gene expression profiles of motor and autophagic cellular cascades and inflammatory/angiogenic responses were all inhibited, favoring adoption of an anti-migratory phenotype. Like ROCK inhibition, tissue engineered bioscaffolds can influence the extracellular matrix. We built upon our evidence that astrocytes maintained on 3D poly-ε-caprolactone (PCL) electrospun scaffolds adopt a cytotrophic phenotype similar to that produced by Fasudil. Using these procedures, employing mature 3D cultured astrocytes, Fasudil (100 μM) or Y27632 (30 μM) added for the last 72 h of culture altered arborization, which featured numerous additional minor processes as shown by GFAP and AHNAK immunolabelling. Both ROCK inhibitors decreased F-actin, but increased G-actin labeling, indicative of disassembly of actin stress fibers. ROCK inhibitors provide additional beneficial effects for bioengineered 3D astrocytes, including enlargement of the overall arbor. Potentially, the combined strategy of bio-compatible scaffolds with ROCK inhibition offers unique advantages for the management of glial scarring. Overall these data emphasize that manipulation of the astrocyte phenotype to achieve a "healthy biology" offers new hope for the management of inflammation in neuropathologies.
dc.languageEnglish
dc.publisherFRONTIERS MEDIA SA
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTranscriptomic analysis and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis
dc.typeJournal Article
dc.identifier.doi10.3389/fnins.2015.00050
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleFrontiers in Neuroscience
melbourne.source.volume9
melbourne.source.issueFEB
melbourne.identifier.nhmrc1020401
melbourne.identifier.nhmrc1019833
dc.rights.licenseCC BY
melbourne.elementsid1079738
melbourne.contributor.authorHorne, Malcolm
melbourne.contributor.authorBeart, Philip
dc.identifier.eissn1662-453X
melbourne.identifier.fundernameidNHMRC, 1020401
melbourne.identifier.fundernameidNHMRC, 1019833
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record