DECREASED NEUROFILAMENT GENE-EXPRESSION IS AN INDEX OF SELECTIVE AXONAL HYPOTROPHY IN AGING

AXONAL atrophy may reflect earlier and more reversible events in neuro degeneration and ageing than somatic atrophy. Innervation density by s ympathetic fibres from the rat superior cervical ganglion (SCG) to the middle cerebral artery (MCA) decreases dramatically in old age, while that to the iris is largely unchanged. In situ hybridization las used in conjunction with retrograde tracers to examine the role of the neu ronal cytoskeleton in this selective axonal vulnerability. Using a rib oprobe complementary to neurofilament light chain (NF-L) mRNA, there w as a 22-25% decrease in the mean grain density in aged neurones when a ll neurones were examined. A small subset of these neurones was shown to project to the MCA and another to the iris. In young SCG, both subp opulations expressed intermediate grain densities for NF-L mRNA. In MC A-projecting neurones, there was a 40% decline in grain density with a geing (p<0.05), with no change in iris-projecting neurones. Our result s demonstrate that major decreases in NF-L expression may represent ce llular markers of selective axonal hypotrophy by aged neurones.