Avtor/Urednik		Keller, Simona; Sarchiapone, Mardo; Zarrilli, Federica; Videtič, Alja; Ferraro, Angelo; Carli, Vladimir; Balažic, Jože; Marušič, Andrej
Naslov		Increased BDNF promoter methylation in the wernicke area of suicide subjects
Tip		članek
Vir		Arch Gen Psychiatry
Vol. in št.		Letnik 67, št. 3
Leto izdaje		2010
Obseg		str. 258-67
Jezik		eng
Abstrakt		Context: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in the pathophysiology of suicidal behavior and BDNF levels are decreased in the brain and plasma of suicide subjects. So far, the mechanisms leading to downregulation of BDNF expression are poorly understood. Objectives: To test the hypothesis that alterations of DNA methylation could be involved in the dysregulation of BDNF gene expression in the brain of suicide subjects. Design: Three independent quantitative methylation techniques were performed on postmortem samples of brain tissue. BDNF messenger RNA levels were determined by quantitative real-time polymerase chain reaction. Setting: Academic medical center. Patients or Other Participians: Forty-four suicide completers and 33 nonsuicide control subjects of white ethnicity. Main outcome measures:The DNA methylation degree at BDNF promoter IV and the genome-wide DNA methylation levels in the brain's Wernicke area. Results: Postmortem brain samples from suicide subjects showed a statistically significant increase of DNA methylation at specific CpG sites in BDNF promoter/exon IV compared with nonsuicide control subjects (P < .001). Most of the CpG sites lying in the -300/+500 region, on both strands, had low or no methylation, with the exception of a few sites located near the transcriptional start site that had differential methylation, while genome-wide methylation levels were comparable among the subjects. The mean methylation degree at the 4 CpG sites analyzed by pyrosequencing was always less than 12.9% in the 33 nonsuicide control subjects, while in 13 of 44 suicide victims (30%), the mean methylation degree ranged between 13.1% and 34.2%. Higher methylation degree corresponded to lower BDNF messenger RNA levels. (Abstract truncated at 2000 characters)
Deskriptorji		SUICIDE BRAIN-DERIVED NEUROTROPHIC FACTOR TEMPORAL LOBE DNA METHYLATION RNA, MESSENGER POLYMERASE CHAIN REACTION AUTOPSY