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

Abstract

Background 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. Materials and methods 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. Results 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. Conclusions 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

Neurobiological Basis of Increased Risk for Suicidal Behaviour

“…Data indicate lower mRNA levels of BDNF and its receptor TrkB in the prefrontal cortex and hippocampus in suicide patients [74][75][76]. Moreover, downregulation of BDNF in the anterior cingulate cortex and amygdala, and lower serum BDNF levels, have been reported in depressed patients with suicidal intentions as compared with depressed patients without suicidal intentions [30,73,75]. Lower levels of BDNF in suicidal patients are probably the consequence of epigenetic modifications due to stress [75,76].…”

“…Suicidal patients are characterised by abnormal neuroplasticity [23,73]. Data indicate lower mRNA levels of BDNF and its receptor TrkB in the prefrontal cortex and hippocampus in suicide patients [74][75][76]. Moreover, downregulation of BDNF in the anterior cingulate cortex and amygdala, and lower serum BDNF levels, have been reported in depressed patients with suicidal intentions as compared with depressed patients without suicidal intentions [30,73,75].…”

“…Moreover, downregulation of BDNF in the anterior cingulate cortex and amygdala, and lower serum BDNF levels, have been reported in depressed patients with suicidal intentions as compared with depressed patients without suicidal intentions [30,73,75]. Lower levels of BDNF in suicidal patients are probably the consequence of epigenetic modifications due to stress [75,76]. Some data suggest that serum levels of BDNF could be a promising marker of suicide [76], but others deny this finding [73].…”

Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression

“…Antidepressants and exercise increase endogenous BDNF in rodents, resulting in enhanced neurogenesis, reduced neuronal apoptosis, and inhibition of stress-induced depressive-like behaviors [92], while reduced BDNF is associated with depression as well as other neuropsychiatric and neurologic diseases such as Parkinson's disease and Alzheimer's disease [91]. Further, lower BDNF levels are observed in the PFC and the hippocampus of suicide victims compared to non-victims of suicide with or without depression [93].…”

Serum BDNF and suicidal ideation in drug-naïve and drug-treated MDD patients: a case–control study

“…Postmortem examinations of completed suicides reveal lower BDNF levels in the hippocampus and prefrontal cortex but no alterations in the entorhinal cortex or amygdala. It is worth mentioned that patients who had experienced early childhood trauma and/or committed suicide had reduced BDNF levels in the anterior cingulate cortex than no suicidal subjects with no reported childhood trauma [60].…”