NGF expression in the aged XXXX pineal gland does not correlate with loss of sympathetic axonal branches and varicosities.

@entity35 @entity669 @entity194
The factors that determine the ability of some, but not all neurons, to sustain their axonal projections during aging remain largely unknown. Because sympathetic neurons remain responsive to nerve growth factor (NGF) in old age, it has been proposed that the selective decrease observed in the sympathetic innervation to some targets in aged @entity35 may be the result of a deficit in target-derived NGF. In this study we utilized two different techniques to demonstrate decreased target innervation by sympathetic fibers in the aged @entity35 pineal gland, which is an appropriate and relevant model for examining mechanisms of neuron-target interactions in aging. @entity669 hydroxylase immunoreactive profiles were quantified in pineal glands of young and aged male @entity35 . The density of @entity669 hydroxylase-immunoreactive fibers was 30% lower in aged pineals, although the remaining fibers contained 20% more @entity669 hydroxylase-immunoreactivity. Othograde tracing of the pineal sympathetic innervation using biotinylated dextran revealed that average axon length, varicosity numbers, branch point numbers, and numbers of terminations were all decreased by approximately 50% in aged tissues, indicating possible functional deficits. These findings suggest that whole branches, along with their associated varicosities were lost in old age. A sensitive quantitative ribonuclease protection assay and a two-site ELISA assay were used to examine whether reduced NGF availability might correlate with sympathetic nerve @entity194 . No significant differences were detected in either NGF mRNA or NGF protein levels when comparing young and aged pineal glands, suggesting that @entity194 in aged sympathetic neurons is not causally related to reduced availability of NGF at the target. Our results indicate that mechanisms other than NGF expression need to be explored in order to explain the age-related axonal regression observed in this target.
