Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

Abstract

Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of longterm memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/ CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.

Microinjection of histone deacetylase inhibitor into the ventrolateral orbital cortex potentiates morphine induced behavioral sensitization

“…However, some of the effects of inhibition of histone acetyltransferases in plasticity have been mediated by transcription-dependent and -independent mechanism (Merschbaecher et al, 2016). In addition, nonhistone, maybe even cytoplasmic substrates (STAT, NF-B, importin-) probably participate in the neuronal and behavioral plasticity.…”

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

“…Reactivated memories were affected by garcinol which displayed long‐lasting effects and, thus, garcinol can support drug abstinence and be a suitable therapy for psychopathologies such as drug addiction. Indeed, memory processes in honeybees strongly depend on HAT activity and histone H3 acetylation by treatment with garcinol or C646 …”

“…Indeed, memory processes in honeybees strongly depend on HAT activity and histone H3 acetylation by treatment with garcinol or C646. [89]…”

Sodium butyrate modulates a methamphetamine‐induced conditioned place preference

“…Histone acetylation is a crucial modulating mechanism underlying the activation of gene transcription, which is necessary for the formation of memory (Alberini, 2009;Guan et al, 2009;McQuown et al, 2011;Kim et al, 2012;Merschbaecher et al, 2016). Additionally, HDAC inhibitors were found to enhance synaptic plasticity and long-term memory (Bredy and Barad, 2008;Guan et al, 2009).…”