Gene expression in age-related degeneration of the nervous system

The goal of this study was to gain a better understanding of the molecular basis of age-related degeneration of the nervous system. The relationship between aging and gene expression for a series of proteins involved in nervous system structure and function was determined. Run-on transcription assays were used to evaluate gene-specific transcription rates in rat forebrain with aging and in Alzheimer's disease (AD), a common neurodegenerative disease of the elderly. Northern blot and in situ hybridizations were used to evaluate mRNA levels in rat forebrain and dorsal root ganglia (DRG) with aging and following axotomy.; An age-related decrease in neurofilament (Nf) expression was detected in rat brain and DRG. The decrease in the brain was attributed to decreased Nf transcription. The decrease in the DRG was associated with decreased Nf protein and axonal and perikaryal atrophy. These results indicate that a failure to maintain homeostatic rates of Nf transcription may be the cause of neuronal atrophy in the aging nervous system.; An age-related increase in glial fibrillary acidic protein (GFAP) expression was detected in aging rat and AD brain which is consistent with previous studies. This increase was shown to be due to an increase in GFAP transcription demonstrating for the first time that GFAP transcription is upregulated in aging and degenerating brain. The increase in GFAP expression is a molecular marker for astrogliosis and there is evidence that astrogliosis may exacerbate age-related degeneration of the brain.; Amyloid precursor protein (APP) expression appeared to increase in aging rat brain, at least in some animals, whereas growth associated protein-43 (GAP-43/B-50) was maintained in aging rat DRG. These proteins are associated with growth and repair of neurons and an age-related increase in expression may indicate compensatory sprouting by surviving neurons into areas denervated by the aging process.; Nerve growth factor (NGF) receptor expression decreased in rat DRG with aging and following axotomy. Previous studies have shown that NGF upregulates NGF receptor expression. Taken together, these results suggest that an age-related decline in target-derived NGF may lead to decreased expression of NGF receptor in responsive neurons and thus decreased sensitivity of these neurons to NGF.