Events during the early life of rodents have been shown to have a marked effect on mental and physical health in adulthood. In particular mood and cognitive abilities can be adversely altered following prolonged periods of infant-mother separation. Animals experiencing such a maternal deficit during their early days later suffer from extreme hypersensitivities to certain stress-inducers. The recently published work of one group at the Max-Planck Institute Of Psychiatry in Germany has now drawn a direct link between such behavioral anomalies and the methylation state of well-defined regions of DNA.

More specifically, infant-mother separation caused a reduction in methylation of enhancers for the Adrenocorticotropin (AVP) hormone gene increasing the expression of AVP and ultimately disturbing brain endocrine hormone function. The resulting phenotypic changes were remarkable- a significant loss of memory and decreased mobility. Encouragingly these changes could be partially reversed using AVP receptor agonists- a finding that could have important medical ramifications given that these same enhancer regions are to be found across species including humans.

“This is the first study to depict a molecular mechanism by which stress early in life can cause effects later in life” noted McGill University epigeneticist Moshe Szyf in an interview with The Scientist magazine. The so-called hypomethylation of the AVP enhancer region was specific to an area of the brain that is intimately involved in stress related hormone release. The Max-Planck group further characterized the methylation enzymes, notably a protein by the name of MeCP2, whose activities have been irreversibly impacted.

Chris Murgatroyd, Alexandre V Patchev, Yonghe Wu, Vincenzo Micale, Yvonne Bockmühl, Dieter Fischer, Florian Holsboer, Carsten T Wotjak, Osborne F X Almeida & Dietmar Spengler (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress, Nature Neuroscience, published online 8 November 2009; doi:10.1038/nn.2436

Jef Akst (2009) Early Stress Alters Epigenome, The Scientist, Posted on 8th November, See http://www.the-scientist.com/blog/display/56139/