Age-dependent alterations in nerve growth factor (NGF)-related proteins, sortilin, and learning and memory in rats.

The objective of this study was to evaluate the effects of aging on the performance of specific memory-related tasks in rats as well as to determine the levels of several nerve growth factor (NGF)-related proteins in relevant brain regions. The results indicated age-related impairments in spatial learning in a water maze task as well as deficits in recognition memory in a Spontaneous Novel Object Recognition task. In the prefrontal cortex and hippocampus, aged rats (compared to young controls) had elevated levels of the proneurotrophin, proNGF (+1.8-1.9 fold), p75(NTR) receptors (+1.6-1.8 fold) and sortilin (+1.8-2.1 fold), and decreased levels of mature NGF (-36 to 44%), and phospho-TrkA receptors (-45 to 49%). The results of this study support the argument that NGF signaling is altered in the aging brain, and that such alterations may contribute to an age-related decline in cognitive function. These results may also help to identify specific components of the NGF-signaling pathway that could serve as targets for novel drug discovery and development for age-related disorders of cognition (e.g., Alzheimer's disease).