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. Disclosure of potential conflicts of interest is found at the end of this article.
Widestrand
Asa
A
Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Medicinaregatan 9A, SE-413 90 Göteborg, Sweden.
Faijerson
Jonas
J
Wilhelmsson
Ulrika
U
Smith
Peter L P
PL
Li
Lizhen
L
Sihlbom
Carina
C
Eriksson
Peter S
PS
Pekny
Milos
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000166:cytology; D018920:Coculture Techniques; D016654:Genes, RAG-1; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency* / Q000235:genetics; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D006085:Graft Survival; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D009474:Neurons / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology; D051381:Rats; D014746:Vimentin / Q000172:deficiency* / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin