Epigenetic marks and their relationship with BDNF in the brain of suicide victims

Suicide is a common phenomenon affecting people of all ages. There is a strong relationship between suicidal ideation and depressive disorders. Increasing number of studies suggest that epigenetic modifications in certain brain areas are the main mechanism through which environmental and genetic factors interact with each other contributing to the development of mental disorders. To verify this hypothesis, some epigenetic marks: H3K9/14ac, HDAC2/3, H3K27me2 and Sin3a, as well as p-S421-MeCP2/MeCP2 were examined. On the other hand, BDNF protein level were studied.

Western blot analysis were performed in the frontal cortex (FCx) and hippocampus (HP) of suicide victims (n = 14) and non-suicidal controls (n = 8). The differences between groups and correlations between selected proteins were evaluated using Mann-Whitney U-test and Spearman's rank correlation.

Statistically significant decrease in H3K9/14ac (FCx:↓~23%;HP:↓~33%) combined with increase in HDAC3 (FCx:↑~103%;HP:↑~85% in HP) protein levels in suicides compared to the controls was shown. These alterations were accompanied by an increase in H3K27me2 (FCx:↑45%;HP:↑~59%) and Sin3a (HP:↑50%) levels and decrease in p-S421-MeCP2/MeCP2 protein ratio (HP:↓~55%;FCx:↓~27%). Moreover, reduced BDNF protein level (FCx:↓~43%;HP:↓~28%) in suicides was observed. On the other hand, some significant correlations (e.g. between H3K9/14ac and HDAC2 or between BDNF and p-S421-MeCP2/MeCP2) were demonstrated.

Our findings confirm the role of epigenetic component and BDNF protein in suicidal behavior. Lowered BDNF protein level in suicides is probably due to decrease in histone acetylation and increased level of factors related with deacetylation and methylation processes, including MeCP2 factor, which may operate bidirectionally (an activator or inhibitor of transcription).