Journal article

Transcriptomic analysis and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis

Ross D O'Shea, Chew L Lau, Natasha Zulaziz, Francesca L Maclean, David R Nisbet, Malcolm K Home, Philip M Beart

FRONTIERS IN NEUROSCIENCE | FRONTIERS MEDIA SA | Published : 2015

Abstract

Astrocytes 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 p..

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Grants

Awarded by NHMRC Project Grant


Awarded by NHMRC Career Development Fellowship


Awarded by NHMRC Research Fellowships


Funding Acknowledgements

This research was supported by funding from an NHMRC Project Grant (APP 1020332). DN was supported by an Australian Research Council Australian Postdoctoral Fellowship and subsequently by an NHMRC Career Development Fellowship (APP1050684). MH and PB were supported NHMRC Research Fellowships, APP 1020401 and APP 1019833, respectively. Access to the facilities of the Centre for Advanced Microscopy (CAM) with funding through the Australian Microscopy and Microanalysis Research Facility (AMMRF) is gratefully acknowledged. The Florey Institute of Neuroscience and Mental Health receives infrastructure support from the Victorian State Government (Australia).