Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have 
been linked with memory, stress, and neuropsychiatric disorders. Here we 
examined whether there was a link between an established rat model of 
post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. Adult male 
Sprague-Dawley rats were given psychosocial stress composed of two acute cat 
exposures in conjunction with 31 days of daily social instability. These 
manipulations have been shown previously to produce physiological and behavioral 
sequelae in rats that are comparable to symptoms observed in traumatized people 
with PTSD. We then assessed Bdnf DNA methylation patterns (at exon IV) and gene 
expression. We have found here that the psychosocial stress regimen 
significantly increased Bdnf DNA methylation in the dorsal hippocampus, with the 
most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, 
the psychosocial stress regimen significantly decreased methylation in the 
ventral hippocampus (CA3). No changes in Bdnf DNA methylation were detected in 
the medial prefrontal cortex or basolateral amygdala. In addition, there were 
decreased levels of Bdnf mRNA in both the dorsal and ventral CA1. These results 
provide evidence that traumatic stress occurring in adulthood can induce CNS 
gene methylation, and specifically, support the hypothesis that epigenetic 
marking of the Bdnf gene may underlie hippocampal dysfunction in response to 
traumatic stress. Furthermore, this work provides support for the speculative 
notion that altered hippocampal Bdnf DNA methylation is a cellular mechanism 
underlying the persistent cognitive deficits which are prominent features of the 
pathophysiology of PTSD.