84 Mouse models have been very useful in delineating the relationship between disturbances to MeCP2 and the disease.85 In mice, deletion of MeCP2 mimics RTT syndrome, leading to locomotor impairments and reductions in brain size.86,87 Mice with a truncated MeCP2 protein, similar to that of RTT patients, developed many features of RTT, such as tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions; these mice

also presented hyperacetylation Inhibitors,research,lifescience,medical on histone H3,88 HDAC activation illustrating that chromatin abnormalities exist in this disorder. In astrocytes cultured from a mouse model of RTT, MeCP2 deficiency causes significant abnormalities in BDNF regulation, cytokine production, and neuronal dendritic induction. Whereas previous experiments have only focused on neurons, this evidence suggests that astrocytes may also represent therapeutic targets for RTT89 The classic Inhibitors,research,lifescience,medical form of autism also appears to be connected to MeCP2 expression. Coding mutations affecting the protein are rarely detected in autism, but significantly increased MeCP2 promoter methylation has been found in autistic male frontal cortex compared with controls, and this inversely correlated with protein expression90; aberrant promoter methylation

at MeCP2 has also been detected Inhibitors,research,lifescience,medical in female brain DNA.91 Similarly, loss of methyl-CpG binding protein 1 (MBD1), leads to autismlike behavioral deficits in mice, namely reduced social interaction, learning deficits, anxiety, defective Inhibitors,research,lifescience,medical sensory motor gating, depression, and abnormal brain serotonin activity.92 Also, a novel mutation has been discovered in the Jumonji AT-rich interactive domain 1C (JARID1C) gene of a child with autism. While very preliminary, this discovery is interesting, as JARID1C is believed to be a histone demethylase specific for di- and trimethylated histone 3 lysine 4 (H3K4), as well as a transcriptional repressor for the ASD-associated genes SCN2A, CACNA1H, BDNF, and SLC18A1.93 Finally, another interesting

Inhibitors,research,lifescience,medical hypothesis relating epigenetics to ASD concerns the observation that autistic children exhibit improved behavior communication during febrile episodes.94 It may be the case that fever restores the modulatory functions of the intact, Linifanib (ABT-869) but dysregulated locus coeruleus-noradrenergic (LC-NA) system that is present in ASD. The fact that the state of the LC-NA system can be switched back and forth, combined with evidence that imprinted genes within the LC-NA are tightly epigenetically regulated and susceptible to environmental interference,95 suggests that dynamic epigenetic remodeling processes may regulate the malfunctioning pathways in ASD.96 Epigenetic treatment opportunities Epigenetic drug strategies are currently employed to treat a collection of cancer subtypes, and these medications are now being considered in the treatment of psychiatric disease, as well.