Neuronal plasticity in aging: a quantitative immunohistochemical study of GAP-43 distribution in discrete regions of the rat brain.

Age-related changes in neuroplasticity have been investigated considering the neuronal growth-associated protein GAP-43 as a marker of nerve cell structural adaptive capabilities. We carried out a quantitative immunohistochemical study on the distribution of GAP-43 in the molecular layer of the cerebellar cortex, in the inner molecular layer of the hippocampal dentate gyrus, in the stratum radiatum of the CA1 region, in layer 1 of the cingulate cortex and in the nerve fiber layer of the main olfactory bulb of 3-, 18- and 31-month-old Wistar rats. A decrease of GAP-43 immunoreactivity was observed in the old rats in comparison with the adult animals in all the 5 areas analyzed, although these variations were only statistically significant in the dentate gyrus, cingulate cortex and olfactory bulb. In these latter zones, GAP-43 immunolabeling is reduced by 54, 42 and 38%, respectively, in the old versus the adult group. Comparing these data with the age-dependent decrease of neuron density innervating the areas investigated, we support the hypothesis that the decline of GAP-43 observed in old animals documents a consistent reduction of axon plasticity in the inner molecular layer of the dentate gyrus and in layer 1 of the cingulate cortex. These results suggest an important role of GAP-43 as a marker of age-dependent deterioration of synaptic plasticity, especially in those areas of the brain involved in memory and emotional behavior.