Histone deacetylase 3 inhibition re-establishes synaptic tagging and capture in aging through the activation of nuclear factor kappa B

Abstract

Aging is associated with impaired plasticity and memory. Altered epigenetic mechanisms are implicated in the impairment of memory with advanced aging. Histone deacetylase 3 (HDAC3) is an important negative regulator of memory. However, the role of HDAC3 in aged neural networks is not well established. Late long-term potentiation (late-LTP), a cellular correlate of memory and its associative mechanisms such as synaptic tagging and capture (STC) were studied in the CA1 area of hippocampal slices from 82-84 week old rats. Our findings demonstrate that aging is associated with deficits in the magnitude of LTP and impaired STC. Inhibition of HDAC3 augments the late-LTP and re-establishes STC. The augmentation of late-LTP and restoration of STC is mediated by the activation of nuclear factor kappa B (NFκ B) pathway. We provide evidence for the promotion of associative plasticity in aged neural networks by HDAC3 inhibition and hence propose HDAC3 and NFκ B as the possible therapeutic targets for treating age -related cognitive decline.