Toward understanding of the molecular basis of loss of neuronal plasticity in ageing

Although there are several lines of evidence which suggest that neuronal plasticity decreases in some regions of both the central and peripheral nervous systems as well as in neuroendocrine tissues during development and ageing, the molecular mechanisms underlying loss of plasticity are largely unknown. To explore this question, we examined changes in expression profiles of neuronal growth-associated proteins (nGAPs) during ageing as well as the molecular regulatory mechanisms of their induction by nerve growth factor (NGF). SCG10, one of the nGAPs, is expressed in subsets of central neurons which maintain a high degree of plasticity in the adult, and is induced after neuronal deafferentation. This is a basis for analysing if SCG10 is involved in the remodelling of adult neurons during reactive synaptogenesis in diseased brains as well as in normal ageing. Studies of the induction of SCG10 by NGF in PC12 cells suggest that transcriptional inducible element(s) are present, at least in part, in the upstream region of the SCG10 gene. These studies of the regulation of nGAPs in ageing brains and neuroendocrine cells may yield new insights on reactivating neurites of partially degenerated neurons in the ageing brain.