Research

Neurotrophin signalling and selective neuronal vulnerability protects neurons from cell death.

1.

Early experiments showed that trophic interactions between neurons and their peripheral 'target tissues', known to be vital for the appropriate development of neurons, remain crucial contributors to the health and plasticity of adult and ageing neurons. A number of factors, including the neurotrophin family of neurotrophic factors, are known to be present in adult as well as developing target tissues to fulfill this role. During maturation, neurons retain and may even increase their capacity to grow in response to target-derived neurotrophic factors. However, during maturation, these neurons lose their earlier dependence for survival on neurotrophic factors. A recent study has shown that the induction of neurotrophin-independent survival is crucially dependent on PI3-kinase signalling. Survival and growth thus come to be separately regulated in adulthood, providing a mechanism which protects neurons cell death following injury whilst enabling them to continue to respond to altered functional demand.

Legend

1A. sympathetic nerve supply to the iris of young (3-6wk) and old (24m) rats. Note there is no reduction in nerve density in old age; in fact ageing irideal nerves continue to grow.
1B. sympathetic nerve supply to the middle cerebral artery (MCA) in young and old (24m) rats. Note the substantial reduction (about 50%) in the density of nerve fibres.
1C. sympathetic neurons from the superior cervical ganglion projecting to MCA in young and old rats, filled with neurobiotin and imaged using confocal microscope. Note blunted, shortened dendrites, also characteristic background staining due to 'age pigment' (lipofuscin, a product of oxidative damage) in the old ganglion.
1D. enteric neurons of the myenteric plexus of the ileum from young and old (16m) rats. The young ganglion is packed with neurons while the old example shows numerous empty holes demonstrating sites of neuron loss.

Continue to research page two......