Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur, India.
Brain Res Bull. 2019 Aug;150:86-101. doi: 10.1016/j.brainresbull.2019.05.011. Epub 2019 May 17.
Histone deacetylases (HDACs) regulate gene expression epigenetically through synchronized removal of acetyl groups from histones required towards memory consolidation. Moreover, dysregulated epigenetic machinery during fear or extinction learning may result in altered expression of some of these genes and result in Post Traumatic Stress Disorder (PTSD). In the present study, region-specific expression of Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC2) was correlated to the acetylation of histones H3 and H4 and the resultant conditioned response, in rats undergone fear and extinction learning. The neuronal activation, histone acetylation at H3/H4 and expression of HDAC1/HDAC2 in centrolateral amygdala (CeL) and centromedial amygdala (CeM) of central Amygdala (CeA) and prelimbic (PL) and infralimbic (IL) of Prefrontal cortex (PFC) were found to be associated in a differential manner following fear and extinction learning. Moreover in CeM, the main output of the fear circuitry, the level of HDAC1 was down-regulated following conditioning and up-regulated following extinction as opposed to which HDAC2 was down-regulated in CeM following conditioning but not following extinction. Furthermore, in CeL the HDAC1 was upregulated and HDAC2 was downregulated following conditioning and extinction. This has important implications in speculating of the role of HDACs in fear memory consolidation and its extinction.
组蛋白去乙酰化酶(HDACs)通过同步从组蛋白上除去乙酰基来调节基因表达的表观遗传,这对于记忆巩固是必需的。此外,在恐惧或消退学习过程中,表观遗传机制失调可能导致这些基因的表达发生改变,并导致创伤后应激障碍(PTSD)。在本研究中,特定区域的组蛋白去乙酰化酶 1(HDAC1)和组蛋白去乙酰化酶 2(HDAC2)的表达与组蛋白 H3 和 H4 的乙酰化以及随后的条件反应相关,这些大鼠经历了恐惧和消退学习。在中央杏仁核(CeA)的中心外侧杏仁核(CeL)和中央杏仁核(CeM)以及前额叶皮层(PFC)的前扣带皮层(PL)和下边缘皮层(IL)中,神经元的激活、组蛋白 H3/H4 的乙酰化以及 HDAC1/HDAC2 的表达与恐惧和消退学习后的差异方式相关。此外,在恐惧回路的主要输出 CeM 中,HDAC1 的水平在条件作用后下调,在消退后上调,而在 CeM 中,HDAC2 在条件作用后下调,但在消退后没有下调。此外,在 CeL 中,HDAC1 在条件作用和消退后上调,HDAC2 在条件作用和消退后下调。这对于推测 HDACs 在恐惧记忆巩固及其消退中的作用具有重要意义。