title: Functional and morphological effects of NG2 proteoglycan deletion on hippocampal neurogenesis.
abstract: NG2-expressing cells are the largest proliferating cell population in the adult central nervous system. The function of NG2 proteoglycan or NG2-expressing cells in the adult brain, however, is unknown. So far, NG2-positive cells are thought to be mainly oligodendrocyte precursor cells. This view was recently challenged when NG2+/CNP-EGFP-positive cells were identified as multipotent progenitor cells in the postnatal and adult CNS (e.g., [Belachew, S., Chittajallu, R., Aguirre, A.A., Yuan, X., Kirby, M., Anderson, S., Gallo, V., 2003. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J. Cell Biol. 161, 169-186]). In addition, purified NG2-expressing progenitor cells, were shown to differentiate into neurons and astrocytes in vitro [Sellers, D.L., Horner, P.J., 2005. Instructive niches: environmental instructions that confound NG2 proteoglycan expression and the fate-restriction of CNS progenitors J. Anat. 207, 727-734]. In this study, we focus on the influence of NG2 ablation on neurogenesis in the hippocampus, where putative multipotent NG2-positive cells reside, and on hippocampus-dependent behavior using NG2 knockout mice. Using the thymidine analogue bromodeoxyuridine (BrdU) to label dividing cells in vivo we show that the number of BrdU-positive cells was unchanged in the hippocampus of NG2 knockout mice 1 day after a series of BrdU injections. This finding suggests that the proliferation rate of hippocampal progenitor cells is not influenced by NG2. A few BrdU-positive cells were found in deeper layers of the granule zone 1 day after a series of BrdU injections, which is different from the wild type. The presence and the phenotype of newborn hippocampal cells were studied 4 weeks after a series of BrdU injections. The survival and differentiation of BrdU-positive cells in NG2 knockout hippocampus did not significantly differ from wild-type mice. Concurrently, the water maze task did not reveal obvious differences compared to wild-type animals. These results suggest that the null mutation for NG2 does not influence adult hippocampal neurogenesis or hippocampal-dependent behavioral tasks.
authors.affiliation: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. thallmair@hifo.unizh.ch
authors.forename: Michaela
authors.initials: M
authors.lastname: Thallmair
authors.forename: Jasodhara
authors.initials: J
authors.lastname: Ray
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D011509:Proteoglycans / Q000172:deficiency / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D013550:Swimming / Q000502:physiology; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D001973:Bromodeoxyuridine; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4