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First published online July 12, 2007
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2007-0122v1
25/10/2619    most recent
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Submitted on February 12, 2007
Accepted on June 27, 2007

THE STEM CELL NICHE

Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP-/-Vim-/- mice

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: Milos.Pekny{at}medkem.gu.se.


   Abstract

After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression 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




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M. R. Verardo, G. P. Lewis, M. Takeda, K. A. Linberg, J. Byun, G. Luna, U. Wilhelmsson, M. Pekny, D.-F. Chen, and S. K. Fisher
Abnormal Reactivity of Muller Cells after Retinal Detachment in Mice Deficient in GFAP and Vimentin
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3659 - 3665.
[Abstract] [Full Text] [PDF]




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