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Åsa Widestrand 1, Jonas Faijerson 1, Ulrika Wilhelmsson 1, Peter L. P. Smith 1, Lizhen Li 1, Carina Sihlbom 1, Peter S. Eriksson 1, Milos Pekny 1*
1 Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
* To whom correspondence should be addressed. E-mail: of the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. This response, reactive gliosis, is attenuated in GFAP-/-Vim-/- mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP-/-Vim-/- astrocytes affect the differentiation of neural progenitor cells. In coculture with GFAP-/-Vim-/- astrocytes, neural progenitor cells increased neurogenesis by 65 % and astrogenesis by 124 %. At 35 days after transplantation of neural progenitor cells into the hippocampus, adult GFAP-/-Vim-/- mice had more transplant-derived neurons and astrocytes than wildtype controls, as well as increased branching of neurite-like processes on transplanted cells. Wnt3 immunoreactivity was readily detected in hippocampal astrocytes in wildtype but not in GFAP-/-Vim-/- mice. These findings suggest that GFAP-/-Vim-/- astrocytes allow more neural progenitor cell-derived neurons and astrocytes to survive weeks after transplantation. Thus, reactive gliosis may adversely affect the integration of transplanted neural progenitor cells in the brain.
Key Words. GFAP, vimentin, intermediate filaments, astrocytes, reactive gliosis
