Can the neurotrophic hypothesis explain degeneration and loss of plasticity in mature and ageing autonomic nerves?

Abstract

The causes of age-related degeneration in the peripheral nervous system remain unclear. The search for clues has focused on developmental mechanisms and particularly on the neurotrophic hypothesis and its principal player, nerve growth factor, reduced levels of which are thought to cause degeneration of some autonomic and central neurons in old age. Nerve growth factor may well be important in the mature and ageing nervous system, but recent experiments on sympathetic nerves in ageing rats suggest that lack of NGF is not the only limiting factor in neuronal growth and survival. Other candidates include laminin, which is bound in the extracellular matrix and may act in synergy with NGF to regulate neuronal maintenance and growth in maturity. Reduced, region-specific patterns of availability of one or both of these substances may underlie age-related degeneration in autonomic nerves. Different combinations of these factors may influence particular aspects of neuronal plasticity, such as collateral sprouting and regeneration. In addition to extrinsic factors, it appears increasingly likely that altered neuronal responsiveness to neurotrophic factors in old age contributes to structural and functional deficits in autonomic nerves.