The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning

Abstract

Significance Memory formation relies on a plethora of functions, including epigenetic modifications. Over recent years, multiple studies have indicated the potential of HDAC inhibitors (HDACis) as cognitive enhancers, but their mode of action is not fully understood. Here, we tested whether HDACi treatment improves memory formation via “cognitive epigenetic priming,” stipulating that HDACis—without inherent target specificity—specifically enhance naturally occurring plasticity processes. We found that combining HDACis with fear learning, but not either treatment alone, enhances synaptic plasticity as well as memory-promoting transcriptional signaling in the hippocampus, a brain area recruited by fear learning, but not in unrelated areas. These results lend experimental support to the theory of cognitive epigenetic priming.

Histone deacetylase 9 plays a role in sevoflurane‐induced neuronal differentiation inhibition by inactivating cAMP‐response element binding protein transcription and inhibiting the expression of neurotrophin‐3

“…A major aim of our research was to explore the specific mechanism of action through which sevoflurane inhibits neurogenesis, and we know that HDACs are regulators of tissue development and play an important role in the differentiation of NSCs into neurons in the central nervous system in particular 37 . Previous studies have suggested that anesthetics may modulate the expression of HDACs, 38 and Foquan Luo et al suggested that HDACs may be associated with impaired postoperative learning and memory and dendritic development 39 and that inhibition of HDACs enhances memory 40 . Sevoflurane increases the levels of HDACs in rat hippocampal NSCs and induces neurotoxicity 41 .…”

“…37 Previous studies have suggested that anesthetics may modulate the expression of HDACs, 38 and Foquan Luo et al suggested that HDACs may be associated with impaired postoperative learning and memory and dendritic development 39 and that inhibition of HDACs enhances memory. 40 Sevoflurane increases the levels of HDACs in rat hippocampal NSCs and induces neurotoxicity. 41 Furthermore, it has been shown that HDAC1, HDAC2, and HDAC3 play a major role in memory formation.…”

Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition

“…Histone deacetylases (HDACs) are a family of deacetylation proteases. There are 18 mammalian HDACs in such family, which are divided into four categories based on the homology between HDACs and yeast HDACs: class I HDACs (HDAC1, -2, -3, and − 8); class II HDACs (HDAC4, -5, -6, -7, -9, and − 10); class III HDACs (sirt1–7); and class IV HDAC (HDAC11) [ 49 ]. They can remove the acetyl functional group from the lysine residues at the N-terminus of histones, causing chromatin to bend, allowing DNA to wrap more tightly around histones, which in turn blocks the process of gene transcription.…”

Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease

“…Furthermore, the overexpression or over-representation of HDAC4 in the cytoplasm can recover synaptic transmission [62,63]. There is also evidence that HDAC inhibitor treatments restore brain damage and cognitive performance in AD mice [64][65][66]. The protein product of TRRAP is the only member in the phosphatidylinositol 3-kinase-related kinase (PIKK) family that lacks enzymatic activity.…”