The neural cell adhesion molecule in synaptic plasticity and ageing

By mediating cell adhesion and signal transduction, the neural cell adhesio n molecule (NCAM) regulates neurite outgrowth, fasciculation and target rec ognition in the developing nervous system. In addition, a number of studies suggest an important role for the NCAM in regeneration and learning in the adult nervous system. NCAM-deficient mice are impaired in spatial learning . Moreover, by interfering with normal NCAM function by intracranial inject ions of NCAM-antibodies, long-term potentiation (LTP) in rat hippocampal sl ices and learning in rats and chicks have been inhibited. In the vertebrate nervous system, NCAM is the dominant carrier of polysialic acid (PSA), an unusual carbohydrate consisting of long homopolymers of sialic acid. The PS A-NCAM expression decreases markedly during development. However, an upregu lation of polysialic acid (PSA) in restricted brain areas including the hip pocampus has been observed following learning. Moreover, enzymatic removal of PSA results in impaired LTP and learning. In muscle, the PSA-NCAM expres sion is upregulated following denervation. This response is weakened in agi ng rats. The expression of NCAM and PSA have been shown to be regulated by neuronal activity suggesting that the NCAM may promote structural remodelli ng in an activity dependent manner associated with learning and regeneratio n. (C) 2000. Published by Elsevier Science Ltd. All rights reserved.