title: Distinctive PSA-NCAM and NCAM hallmarks in glutamate-induced dendritic atrophy and synaptic disassembly.
abstract: Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss.
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina; Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis" (IBCN, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Podestá
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Yam
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina; Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis" (IBCN, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Martín Gabriel
authors.initials: MG
authors.lastname: Codagnone
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina; Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis" (IBCN, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Nonthué Alejandra
authors.initials: NA
authors.lastname: Uccelli
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Colman
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina; Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis" (IBCN, CONICET-UBA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Analía
authors.initials: A
authors.lastname: Reinés
mesh_terms: D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; D016708:Synaptophysin; C103469:polysialyl neural cell adhesion molecule; D018698:Glutamic Acid