F2 females derived from the LG/J × SM/J intercross also show an association between Peg3 genotype and maternal performance, thus increasing the likelihood of the participation of this gene in maternal behavior. Peg3 has a high level of sequence similarity
between mice and humans (Kim et al. 1997, 2000), is also imprinted in humans (Murphy et al. 2001), and has a similar protein expression pattern in the brains of both species (Kim et al. 1997), suggesting Inhibitors,research,lifescience,medical conserved functions. Thus, our results further implicate this paternally expressed, maternally imprinted gene in inappropriate maternal behavior. These data also support future studies to investigate human variants and to study associations between Peg3 and nurturing dysfunctions. Acknowledgments We thank R. de Brito and I. Sobrinho Jr for comments and I. M. Watanabe for help in analyzing the results
of the FS test. This study was supported by grants from the Sao Paolo State Inhibitors,research,lifescience,medical Foundation for Research Support (FAPESP: 09/01333–8 to S. C. and 04/14583–9 and 05/56353–2 to A. C. P.). B. S. and G. A. were recipients of FAPESP and CAPES master’s fellowship, respectively. S. C. is a research scholar of CNPq-Brazil.
Stressful events early in life have been widely linked to behavioral phenotypes and have been implicated in the development of psychiatric disorders (Heim and Nemeroff 2001; Inhibitors,research,lifescience,medical Gilman et al. 2003). For instance, early life adversity appears to play a major role in the etiology of depression (Gillespie et al. 2005), and hormones involved in the stress response, including corticotrophin-releasing hormone (CRH) and cortisol, have been shown to be elevated in depressed individuals (Gibbons and Mchugh 1962; Merali et al. 2004). Clearly, Inhibitors,research,lifescience,medical not everyone experiencing stress early in life becomes depressed and it has been suggested Inhibitors,research,lifescience,medical that genetic factors influence susceptibility or resilience to the adverse effects of early life stress (Caspi et al. 2003; Heim et al. 2008). Mounting evidence suggests that these gene–environment interactions
(G × E) may be mediated by epigenetic mechanisms Org 27569 operating at the interface between the genome and the environment (GSK J4 Dolinoy et al. 2007). Changes in DNA methylation following early life stress have been associated with long-term changes in gene expression and behavior (Champagne and Curley 2009) and may contribute to psychiatric disorders (Rutten and Mill 2009) and physiological disturbances (Gluckman et al. 2007) later in life. Recent research using rodent models provides direct evidence for the role of early life stress on the epigenome. Weaver et al. (2004) observed that poor maternal care in rats alters DNA methylation at a specific sequence motif upstream of the glucocorticoid receptor gene (Nr3c1) in the hippocampus of the offspring, directly affecting transcription and subsequent stress responses in adulthood.