title: Polysialic acid limits septal neurite outgrowth on laminin.
abstract: Polysialic acid (PSA) is a large carbohydrate found exclusively on the neural cell adhesion molecule (NCAM). In the adult brain, PSA is re-expressed by septal axons sprouting and regenerating in an environment rich in laminin. Using an in vitro model, we tested the possibility that PSA limits septal outgrowth by preventing maximal interactions with a laminin substrate. Our results indicate that PSA removal from primary septal neurons plated on laminin significantly increased neurite outgrowth at 12 h (14%, p<0.05) and 24 h (22%, p<0.01). In contrast, the removal of PSA had no impact on septal neurite outgrowth on poly-D-lysine. PSA did not influence the plating adhesion of septal neurons on laminin or poly-D-lysine, indicating that the increase in neurite outgrowth caused by PSA removal on laminin is not related to the initial attachment of the neurons to this substrate. Neurite length on laminin was significantly reduced by the function-blocking beta1-integrin antibody in the presence of PSA (20% decrease, p<0.05), and following PSA removal (34% decrease compared to neurites treated with endoN and without the beta1-integrin antibody, p<0.01). Importantly, the beta1-integrin antibody completely abolished the neurite outgrowth promoting effect of PSA removal on laminin. The beta1-integrin antibody had no impact on septal neurite length on poly-D-lysine. Taken together, these results indicate that the removal of PSA from septal neurons increases neurite outgrowth on laminin by promoting interactions between beta1-integrin and laminin.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Burgess
authors.forename: Ying-Qi
authors.initials: YQ
authors.lastname: Weng
authors.forename: Athéna Rebecca
authors.initials: AR
authors.lastname: Ypsilanti
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Cui
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Caines
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubert
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D019922:GAP-43 Protein / Q000378:metabolism; D007797:Laminin / Q000276:immunology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D020665:Septum of Brain / Q000166:cytology*; D012794:Sialic Acids / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000906:Antibodies; D019922:GAP-43 Protein; D007797:Laminin; D012794:Sialic Acids; C021319:polysialic acid