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

After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression of the intermediate filament proteins glial fibrillary acidic protein ( GFAP), vimentin ( Vim), 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 wild-type controls, as well as increased branching of neurite-like processes on transplanted cells. Wnt3 immunoreactivity was readily detected in hippocampal astrocytes in wild-type 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.