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

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-

Aging* ; Memory* ; Neuronal Plasticity*; Hippocampus/*metabolism ; Receptors, Nerve Growth Factor/*metabolism; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Nerve Growth Factor/deficiency

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.
(© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

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Keywords: Late-LTP; aging; hippocampus; p75NTR; synaptic capture; synaptic tagging

0 (Receptors, Nerve Growth Factor)
0 (Ngfr protein, mouse)

Date Created: 20210115 Date Completed: 20210906 Latest Revision: 20231213

20231215

PMC7884039

10.1111/acel.13305

33448137