title: 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 (NFκB) pathway. We provide evidence for the promotion of associative plasticity in aged neural networks by HDAC3 inhibition and hence propose HDAC3 and NFκB as the possible therapeutic targets for treating age -related cognitive decline.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117 597.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore-117 456.
authors.forename: Mahima
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117 597.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore-117 456.
authors.forename: Mahesh Shivarama
authors.initials: MS
authors.lastname: Shetty
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117 597.
authors.forename: Thiruma Valavan
authors.initials: TV
authors.lastname: Arumugam
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117 597.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore-117 456.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D016328:NF-kappa B; D016194:Receptors, N-Methyl-D-Aspartate; D000099186:Histone Deacetylase 3