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Title

Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus

Authors
Djebbara-Hannas, Z.
Durbec, Pascale
Rougon, G.
Published in Proceedings of the National Academy of Sciences. 2000, vol. 97, no. 8, p. 4315-4320
Abstract The neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) contribute to long-term potentiation (LTP) in the CA1 hippocampus. Here we report that the deficient LTP found in slices prepared from NCAM knockout mice and in organotypic slice cultures treated with Endo-N, an enzyme that cleaves the PSA moiety of NCAM, can be rescued by brain-derived neurotrophic factor (BDNF). This effect is not reproduced by nerve growth factor, but can be obtained with high concentrations of NT4/5. The effect of BDNF cannot be accounted for by modifications of N-methyl-D-aspartate receptor-dependent responses or of high-frequency bursts. PSA-NCAM, however, could directly interact with BDNF. Exogenous application of PSA residues or recombinant PSA-NCAM also prevents LTP. Furthermore trkB phosphorylation, and thus BDNF signaling, is reduced in both NCAM knockout mice and Endo-N-treated slice cultures. These results suggest that one action of PSA-NCAM could be to sensitize pyramidal neurons to BDNF, thereby modulating activity-dependent synaptic plasticity.
Keywords AnimalsBrain-Derived Neurotrophic Factor/ physiologyCulture TechniquesHippocampus/metabolism/ physiologyLong-Term Potentiation/ physiologyMiceMice, KnockoutNeural Cell Adhesion Molecules/ geneticsPhosphorylationRatsRats, Sprague-DawleyReceptor, trkB/metabolism
Stable URL http://archive-ouverte.unige.ch/unige:10363
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Identifiers
PMID: 10760298
Structures
Research group Progéniteurs neuronaux
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