IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
artículos
Título:
Distinctive PSA- NCAM and NCAM Hallmarks in Glutamate-Induced Dendritic Atrophy and Synaptic Disassembly
Autor/es:
PODESTÁ MF; YAM P; CODAGNONE MG; UCCELLI NA; COLMAN D; REINÉS A
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2014
ISSN:
1932-6203
Resumen:
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.