Enhancing long-term memory consolidation: HDAC6 inhibition and synaptic protein acetylation

RIVAS S; MILLAN, J.; KRAWCZYK MC; BOCCIA MM; FREUDENTHAL R

SAN LUIS

Congreso; XXXVII Annual Meeting of the Argentinian Society for Neuroscience Research; 2023

SOCIEDAD ARGENTINA DE NEUROCIENCIAS

Histone deacetylases (HDAC) are enzymes that, as a target of inhibition, have been associated with improving memory formation. HDACs’ inhibitors generally used are isotype unspecific. Tubastatin A (TubA) is a specific inhibitor of HDAC6, a mainly cytoplasmic isotype. Here we investigated the effect of TubA on long-term memory consolidation of Inhibitory Avoidance (IA) task in mice and the changes in acetylation levels induced by TubA and by IA training on tubulin acetylation. We found, firstly, an increase in acetylation levels in hippocampal synaptic proteins in extracts made 45 minutes after TubA injection in naive animals. Acetylation was studied by western blot on a ~50 kDa band using an antibody that recognizes acetylated lysines (pan-acetylation) and another that recognizes acetylated lysine 40 from alpha tubulin (K40); both bands overlap. Secondly, that administration of TubA injected intrahippocampal immediately after training facilitates long-term memory consolidation (tested 2 and 8 days post-training). Finally, we found that AI training induces an increase in the pan-acetylation band in hippocampal synaptic proteins but not in K40. These results show that HDAC6 inhibition facilitates long-term memory consolidation and indicate a regulation of synaptic protein acetylation levels during this process. Also suggest that the tubulin acetylation that occurs at the synapse is different from K40.