Effect of Garcinol as a Histone Acetyltransferase Inhibitor on Memory Persistence in Mice

Epigenetic mechanisms have emerged as critical modulators necessary for synaptic plasticity and memory. In particular, histone acetylation has been consistently implicated in memory formation. Garcinol is a naturally occurring compound that functions as a HAT inhibitor. We investigated the effect of post-training systemic administration of Garcinol on memory persistence and histone acetylation levels in the hippocampus of mice. When evaluating NOR memory under a strong training protocol, the results demonstrated that the i.p injection of Garcinol generates a significant memory deficit when animals are tested at 7 days. Conversely, this treatment did not affect long-term memory formation evaluated at 24 hours, suggesting that the amnesic effect is specific to persistence. To elucidate the molecular correlate, acetylation levels in the hippocampus were evaluated one hour after NOR training and Garcinol injection using the Western Blot technique. No significant differences were observed between groups in the acetylation levels of histone H3 or in global acetylation levels. These results indicate that Garcinol selectively affects the persistence, but not the formation of object recognition memory. However, this effect was not accompanied by detectable changes in hippocampal acetylation levels at one hour post-training, raising questions about the temporal window, substrate specificity, or subregional localization of the underlying molecular correlate.