Polysialic acid regulates the clustering, migration, and neuronal differentiation of progenitor cells in the adult hippocampus Journal Article


Authors: Burgess, A.; Wainwright, S. R.; Shihabuddin, L. S.; Rutishauser, U.; Seki, T.; Aubert, I.
Article Title: Polysialic acid regulates the clustering, migration, and neuronal differentiation of progenitor cells in the adult hippocampus
Abstract: Newborn cells of the adult dentate gyrus in the hippocampus are characterized by their abundant expression of polysialic acid (PSA), a carbohydrate attached to the neural cell adhesion molecule (NCAM). PSA+ newborn cells of the dentate gyrus form clusters with proliferating neural progenitor cells, migrate away from these clusters, and terminally differentiate. To identify the roles of PSA in the development of adult progenitors of the dentate gyrus, we injected endoneuraminidase N (endoN) into the hippocampus of adult rats to specifically cleave PSA from NCAM. Two days later, we administered the mitotic marker, 5-bromo-2′-deoxyuridine (BrdU). Three days after BrdU injection, BrdU+ cells were found inside and outside the clusters of newborn cells. In endoN-treated animals, the total number of BrdU+ cells was not changed but significantly more BrdU+ cells were present within clusters, suggesting that PSA normally facilitates the migration of progenitors away from the clusters. Seven days post-BrdU injection, endoN-treated animals had significantly more BrdU+ cells which were also positive for the mature neuronal nuclear marker NeuN compared with controls, indicating that the loss of PSA from progenitor cells increases neuronal differentiation. This report is the first demonstration that PSA is involved in controlling the spatio-temporal neuronal maturation of adult hippocampal progenitors in the normal brain. In vitro, the removal of PSA from adult-derived neural progenitors significantly enhanced neuronal differentiation, strengthening our in vivo findings and indicating that PSA removal on isolated progenitor cells, apart from a complex in vivo environment, induces neuronal maturation. © 2008 Wiley Periodicals, Inc.
Keywords: immunohistochemistry; epidermal growth factor; controlled study; unclassified drug; nonhuman; cell proliferation; ki-67 antigen; animals; animal tissue; cell maturation; microscopy, confocal; animal experiment; neural stem cell; adult stem cells; cell differentiation; neurons; in vitro study; brain development; nerve cell adhesion molecule; polysialic acid; sialidase; rat; cell isolation; cell migration; cell movement; cell count; rats; rats, wistar; analysis of variance; nerve cell differentiation; nervous system development; neuropeptides; migration; fibroblast growth factors; differentiation; sialic acids; broxuridine; bromodeoxyuridine; hippocampus; glycoside hydrolases; microtubule-associated proteins; dentate gyrus; membrane transport proteins; phosphopyruvate hydratase; cell ultrastructure; adult neurogenesis; brdu; endoneuraminidase n
Journal Title: Developmental Neurobiology
Volume: 68
Issue: 14
ISSN: 1932-8451
Publisher: Wiley Periodicals, Inc  
Date Published: 2008-12-01
Start Page: 1580
End Page: 1590
Language: English
DOI: 10.1002/dneu.20681
PUBMED: 18844212
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "Source: Scopus"
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