Age-related changes in hippocampal-dependent synaptic plasticity and memory mediated by p75 neurotrophin receptor.

ABSTRACT: The plasticity mechanisms in the nervous system that are important for learning and memory are greatly impacted during aging. Notably, hippocampal-dependent long-term plasticity and its associative plasticity, such as synaptic tagging and capture (STC), show considerable age-related decline. The p75 neurotrophin receptor (p75^NTR ) is a negative regulator of structural and functional plasticity in the brain and thus represents a potential candidate to mediate age-related alterations. However, the mechanisms by which p75^NTR affects synaptic plasticity of aged neuronal networks and ultimately contribute to deficits in cognitive function have not been well characterized. Here, we report that mutant mice lacking the p75^NTR were resistant to age-associated changes in long-term plasticity, associative plasticity, and associative memory. Our study shows that p75^NTR is responsible for age-dependent disruption of hippocampal homeostatic plasticity by modulating several signaling pathways, including BDNF, MAPK, Arc, and RhoA-ROCK2-LIMK1-cofilin. p75^NTR may thus represent an important therapeutic target for limiting the age-related memory and cognitive function deficits.

SUBMITTER: Wong LW 

PROVIDER: S-EPMC7884039 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature