title: Inhibition of Histone Deacetylase 3 Restores Amyloid-β Oligomer-Induced Plasticity Deficit in Hippocampal CA1 Pyramidal Neurons.
abstract: Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with alterations in epigenetic factors leading to cognitive decline. Histone deacetylase 3 (HDAC3) is a known critical epigenetic negative regulator of learning and memory. In this study, attenuation of long-term potentiation by amyloid-β oligomer, and its reversal by specific HDAC3 inhibitor RGFP966, was performed in rat CA1 pyramidal neurons using whole cell voltage-clamp and field recording techniques. Our findings provide the first evidence that amyloid-β oligomer-induced synaptic plasticity impairment can be prevented by inhibition of HDAC3 enzyme both at the single neuron as well as in a population of neurons, thus identifying HDAC3 as a potential target for ameliorating AD related plasticity impairments.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kumar
authors.initials: K
authors.lastname: Krishna
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnisch
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000633:toxicity*; D010655:Phenylenediamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000201:enzymology; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D000099186:Histone Deacetylase 3
chemical_list: D000178:Acrylamides; D016229:Amyloid beta-Peptides; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D010446:Peptide Fragments; D010655:Phenylenediamines; D000099186:Histone Deacetylase 3; C000603861:RGFP966; C075222:amyloid beta-protein (1-42)
keywords: Amyloid-β oligomer; HDAC3; RGFP966; epigenetics; long-term potentiation; synaptic plasticity