Enhancement of memory consolidation by the histone deacetylase inhibitor sodium butyrate in aged rats

Abstract

Here we show that a systemic injection of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) immediately after training in a step-down inhibitory avoidance task produced an enhancement of memory consolidation that persisted across consecutive retention tests during 14 days in aged rats, while it did not significantly affect memory in young adults. Control aged and young adult rats showed comparable basal levels of memory retention. Our results suggest that HDACis can display memory-enhancing effects specific for aged animals, even in the absence of age-related memory impairment.

Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction

“…Rats were implanted under anesthesia with isoflurane (vaporized in 100% oxygen, at a dose of 5% for induction and 2% for maintenance, in a fraction of 0.5 l/min) with bilateral 8-mm, 23-gauge guide cannulae aimed 1.0 mm above the dorsal hippocampus, as described previously [6,7]. Coordinates (anteroposterior, -4.3 mm from bregma; mediolateral, ±3.0 mm from bregma; ventral, -2.0 mm from skull surface) were obtained from the atlas of Paxinos and Watson [38].…”

“…1. The general procedures for IA behavioral training and retention tests were described in previous reports [6,7] On training trials, the rats were placed on the platform and their latency to step down on the grid with all four paws was measured with a digital chronometer. Immediately after stepping down on the grid, the rats were given a 0.4-mA, 3.0-s footshock and then removed from the apparatus immediately afterward.…”

“…General procedures for intrahippocampal infusions were described in previous reports [6,49,50]. At the time of infusion, a 27-gauge infusion needle was inserted into the guide cannula.…”

“…Agents that preferentially inhibit class I HDACs, such as sodium butyrate (NaB), trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA), relax chromatin structure, which allows for increased readout of genes associated with synaptic plasticity and memory formation, in addition to acting on non-histone targets to stimulate signaling pathways [14,17,39,42]. Pharmacological inhibition of HDACs facilitates long-term potentiation (LTP) in the CA1 area of the dorsal hippocampus, enhances the formation and extinction of memory for fearmotivated tasks [6,9,29,30,55,57], and attenuates memory impairments in aging and models of neurodegenerative disorders [3,8,27,41,44].…”

TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition

“…NaB and other inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid have been shown to enhance LTP and the formation and extinction of memory for fear-motivated tasks (Blank et al 2014;Bredy and Barad 2008;Lattal et al 2007;Levenson et al 2004;Stafford et al 2012;Vecsey et al 2007). We have previously shown that infusions of either NaB or TSA into the dorsal hippocampus given immediately or 3 h after training resulted in a long-lasting enhancement of IA memory (Blank et al 2014), and systemic administration of NaB enhanced memory in aged rats (Blank et al 2015;Reolon et al 2011).…”