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

Abstract

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), p75NTR receptors (+1.6–1.8 fold) and sortilin (+1.8–2.1 fold), and decreased levels of mature NGF (−36–44%), and phospho-TrkA receptors (−45–49%). 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).

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease

“…Terry et al, (2011) showed age-related impairments in spatial learning and deficits in recognition memory. These effects were accompanied by elevated levels of the pro-NGF, p75NTR and sortilin in the prefrontal cortex and hippocampus of aged rats [65].…”

The inorganic perspectives of neurotrophins and Alzheimer's disease

“…This could play a relevant role in the etiology of AD [44,45]. Deficits in TrkA receptor phosphorylation signaling contribute to age-related default in long-term potentiation (LTP) [46][47][48], one of the major cellular mechanisms involved in learning and memory [49]. This can be likely the molecular mechanism for memory impairment in AD.…”

Proteolytic processing of the p75 neurotrophin receptor: A prerequisite for signalling?

“…Interestingly, the expression of p75 NTR and sortilin has often been found to dramatically increase during cell senescence and following nerve injury -situations in which proNGF stimulates apoptosis [50,[56][57][58][59][60]. In line with this, the level of TrkA has also been found to decrease during aging and in association with neuro-degeneration [60,61], changes that would limit activation of a survival signal. Furthermore, proNGF has been reported to up-regulate expression of p75 NTR and sortilin in Schwann cells and natural killer cells [51,59].…”

“…Although controversial, it has also been demonstrated that high concentrations of proNGF can stimulate PC12 cell survival when the p75 NTR /TrkA ratio is low [55]. Interestingly, the expression of p75 NTR and sortilin has often been found to dramatically increase during cell senescence and following nerve injury -situations in which proNGF stimulates apoptosis [50,[56][57][58][59][60]. In line with this, the level of TrkA has also been found to decrease during aging and in association with neuro-degeneration [60,61], changes that would limit activation of a survival signal.…”