Table 4.
Epigenetic mechanism in neuronal disorders.
| Disorder/Disease | Epigenetic modification | Organism and brain region | Mechanism and functions | References |
|---|---|---|---|---|
| Synaptic plasticity | Histone acetylation | Rat, hippocampus | ERK/MAK activity leads to H3K14 hyper-acetylation | Levenson et al., 2004 |
| Rat, amygdala | TSA increases LTP | Yeh et al., 2004 | ||
| Rat, hippocampus | PKC activation enhances LTP and H3K14 acetylation | Miller et al., 2008 | ||
| Mouse, hippocampus | CBP deficiency result in H2B hypo acetylation | Alarcon et al., 2004 | ||
| Mouse, hippocampus | TSA enhances LTP and transcription of CRE | Vecsey et al., 2007 | ||
| Mouse, hippocampus | HDAC2 overexpression impairs, HDAC2 k.o | Guan et al., 2009 | ||
| Mouse, hippocampus | PcGprotein MII-deficiency enhances, TrxG protein and EED deficiency impairs LTP | Kim et al., 2007 | ||
| DNA methylation | Mouse, hippocampus | MBD1 deficiency leads to reduced LTP | Zhao et al., 2003 | |
| Mouse, hippocampus | Inhibition of DNMT1 activity by 5-aza blocks LTP | Levenson et al., 2006 | ||
| Mouse, hippocampus | 5-Aza and zebularine reduce mEPSCs and increase BDNF DNA methylation and transcription | Nelson et al., 2008 | ||
| Mouse, forebrain | Double knock-out DNMT1 and DNMT3a impairs Synaptic plasticity | Feng et al., 2010 | ||
| Seizures | Histone acetylation | Rat, hippocampus | Pilocarpine-induced seizures leads to H4 hypo acetylation of GluR2 | Huang et al., 2002 |
| Rat, hippocampus | Acute and chronic electroconvulsive seizures induce differential H3 and H4 acetylation | Tsankova et al., 2004 | ||
| Schizophrenia | DNA methylation | Human post-mortem brain, cortex region | GAD67 and SOX10 promoter region are hyper methylated correlating with reduced mRNA level | Iwamoto et al., 2005; Guidotti et al., 2007; Huang and Akbarian, 2007 |
| Human post-mortem brain, frontal lobe | COMT promoter is hypo methylated correlating with increased mRNA levels | Abdolmaleky et al., 2006 | ||
| ATRXS | DNA methylation | Human patient-derived cell lines | Mutations in ATRX result in aberrant DNA methylation | Gibbons et al., 2000 |
| Mouse, forebrain | ATRX form a silencing complex with MeCP2 that is disturbed in ATRXS | Kernohan et al., 2010 | ||
| Rett syndrome | DNA methylation | Human lymphocytes mouse, hippocampus, cortex and cerebellum | MeCP2 mutations lead to reduced and CpG islands and acts a transcriptional repressor | Amir et al., 1999; Chen et al., 2001; Collins et al., 2004 |
| DNA methylation and histone acetylation | Mouse, cortex, cerebellum murine cells lines | MeCP2 mutations cause aberrant transcriptionally permissive | Shahbazian et al., 2002; Martinowich et al., 2003 | |
| Histone acetylation and methylation marks | ||||
| Rubinstein Taybi Syndrome | Histone acetylation | Mouse, hippocampus | Reduced global HAT activity due to loss of function in CBP | Oike et al., 1999; Alarcon et al., 2004; Korzus et al., 2004 |
| Fragile X mental retardation | DNA methylation | Human and mouse cell lines | Expansion of CGG or CCG repeats results in aberrant DNA methylation around FMR1 and FMR2 genes | Ashley et al., 1993; Chiurazzi et al., 1998 |
| Alzheimer's | Histone acetylation | Human and mouse cell lines | APP intracellular domain acts as a Notch-like transcription factor associated with HAT TIP60 | Herman et al., 2006; Haberland et al., 2009 |
| Contextual memory Visual cortical plasticity | Histone acetylation/phosphorylation | Crab, central brain | Contextual training increased H3 acetylation | Federman et al., 2009 |
| Mouse, visual cortex region | Visual stimulation increases H3 phosphoacetylation via ERK/MAPK | Putignano et al., 2007 | ||
| Object memory | Histone acetylation | Mouse, hippocampus, forebrain | CBP and p300 deficient mouse have impaired long-term object memory | Alarcon et al., 2004 |
| Histone acetylation/methylation | Muse, hippocampus | Estradiol enhances object memory and increases H3K14 but not H4acetylation | Oliveira et al., 2007; Zhao et al., 2010 | |
| Nuclear inhibition of PP1 increases object memory as well as | ||||
| Mouse, hippocampus | H3K14/H4K5 acetylation, H3K36 trimethylation and H3S100 phosphorylation | Koshibu et al., 2009 | ||
| Fear memory | Histone acetylation | Rat, hippocampus | ERK/MAPK activation increases contextual fear memory and H3 | Chwang et al., 2006 |
| DNA methylation | Mouse, hippocampus | VPA and SB rescue and H3 and H4 hyperacetylation | Dash et al., 2009 | |
| Mouse, hippocampus | CBP deficiency impairs contextual fear conditioning | Wood et al., 2005 | ||
| Rat, hippocampus | Contextual feat training increases BDNF expression and reduce its promoter methylation | Lubin et al., 2008 | ||
| Spatial memory | Histone acetylation | Mouse, hippocampus | CBP deficiency impairs spatial memory accompanied by H2B hypo acetylation. | Alarcon et al., 2004; Korzus et al., 2004 |
| Acetylation/methylation/phosphorylation | Mouse, hippocampus | Nuclear inhibition of PP1 increases spatial memory as well as H3K13/H4K5 acetylation, H3K36 tri-methylation and H3S100 phosphorylation | Koshibu et al., 2009 | |
| Taste memory | Histone acetylation | Mouse, insular cortex | TSA increases H2A and H4 acetylation in brain areas important for taste memories | Swank and Sweatt, 2001 |