title: Depletion of polysialic acid from neural cell adhesion molecule (PSA-NCAM) increases CA3 dendritic arborization and increases vulnerability to excitotoxicity.
abstract: Chronic immobilization stress (CIS) shortens apical dendritic trees of CA3 pyramidal neurons in the hippocampus of the male rat, and dendritic length may be a determinant of vulnerability to stress. Expression of the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in the hippocampal formation is increased by stress, while PSA removal by Endo-neuraminidase-N (endo-N) is known to cause the mossy fibers to defasciculate and synapse ectopically in their CA3 target area. We show here that enzymatic removal of PSA produced a remarkable expansion of dendritic arbors of CA3 pyramidal neurons, with a lesser effect in CA1. This expansion eclipsed the CIS-induced shortening of CA3 dendrites, with the expanded dendrites of both no-stress-endo-N and CIS-endo-N rats being longer than those in no-stress-control rats and much longer than those in CIS-control rats. As predicted by the hypothesis that endo-N-induced dendritic expansion might increase vulnerability to excitotoxic challenge, systemic injection with kainic acid, showed markedly increased neuronal degeneration, as assessed by fluorojade B histochemistry, in rats that had been treated with endo-N compared to vehicle-treated rats throughout the entire hippocampal formation. PSA removal also exacerbated the CIS-induced reduction in body weight and abolished effects of CIS on NPY and NR2B mRNA levels. These findings support the hypothesis that CA3 arbor plasticity plays a protective role during prolonged stress and clarify the role of PSA-NCAM in stress-induced dendritic plasticity.
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York NY 10065, USA.
authors.forename: Trudy
authors.initials: T
authors.lastname: McCall
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weil
authors.forename: Juan
authors.initials: J
authors.lastname: Nacher
authors.forename: Erik B
authors.initials: EB
authors.lastname: Bloss
authors.forename: Abderrahman
authors.initials: A
authors.lastname: El Maarouf
authors.forename: Urs
authors.initials: U
authors.lastname: Rutishauser
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015992:Body Mass Index; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D009930:Organic Chemicals; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000172:deficiency*; D016622:Silver Staining; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D019006:Neural Cell Adhesion Molecules; D009930:Organic Chemicals; D016194:Receptors, N-Methyl-D-Aspartate; D012794:Sialic Acids; C435731:fluoro jade; C021319:polysialic acid; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase; D007608:Kainic Acid