BET proteins inhibitor JQ-1 impaired the extinction of remote auditory fear memory: An effect mediated by insulin like growth factor 2

Inhibiting Brd4 alleviated PTSD‐like behaviors and fear memory through regulating immediate early genes expression and neuroinflammation in rats

“…In addition, treatment with JQ1 could alleviate depression/anxiety‐like behaviors and fear memory and spatial memory impairment, suggesting that Brd4 was involved in the pathophysiological mechanism of PTSD (Benito et al., 2017). However, the effect of inhibiting BET on fear memory was inconsistent in the literature; the promising beneficial effect of JQ1 on memory should be evaluated in the future (Duan et al., 2020; Korb et al., 2015). In addition, this study found no difference in locomotor activity in OFT among experimental groups, consistent with the conclusion that IFS and JQ1 influenced emotion and memory functions but did not affect the spontaneous behaviors (Korb et al., 2017; Wang, Wang, et al., 2018).…”

“…The findings suggested that IEGs directly or indirectly played crucial roles in the forming and maintaining fear memory. In addition, a previous study showed that JQ1 could inhibit the expression of a key set of neuroplasticity‐related genes (i.e., Egr‐2, insulin‐like growth factor 2) in the anterior cingulate cortex of medial PFC and remote fear memory and fear generalization and response in a model of PTSD (Duan et al., 2020). JQ1 administration significantly decreased the expressions of Arc mRNA in the nucleus accumbens induced by cocaine (Guo et al., 2020).…”

“…Recent studies have revealed a critical function for bromodomain‐containing protein 4 (Brd4), member of bromodomain and extra‐terminal domain (BET) protein family (Singh & Sartor, 2020), which interacts with various histone and non‐histone proteins in neuroinflammatory and memory regulation (Duan et al., 2020; Korb et al., 2015; Meng et al., 2014; Wang, Chen, et al., 2019). For instance, Brd4 co‐activates nuclear factor‐kappa B (NF‐κB) by binding to the acetylated RelA subunit (Huang et al., 2009).…”

Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation

“…The involvement of this class of epigenetic readers has been primarily characterized in different types of cancer and inflammatory contexts, due to their role in the transcriptional modulation of oncogenes and immune response mediators [ 13 , 14 ]. However, recent studies highlighted that BET proteins may also play key roles in central nervous system (CNS) homeostasis, regulating the expression of several genes including neurotransmitter receptors, ion channels, and neurotrophic factors [ 15 , 16 , 17 , 18 , 19 ]. Consistently, BET proteins exhibit a high affinity for histone modifications associated with learning and memory processes [ 20 , 21 , 22 ].…”

“…Consistently, BET proteins exhibit a high affinity for histone modifications associated with learning and memory processes [ 20 , 21 , 22 ]. Furthermore, pharmacological inhibition of BET proteins regulates the expression of multiple genes associated with neuroplasticity and cognition [ 15 , 16 , 18 , 23 ]. In this article, we critically review the up-to-date body of knowledge concerning the epigenetic modulation by BET proteins in the physiological processes regulating CNS homeostasis.…”