PMID- 25223586 OWN - NLM STAT- MEDLINE DCOM- 20150514 LR - 20181202 IS - 1365-2869 (Electronic) IS - 0962-1105 (Linking) VI - 24 IP - 2 DP - 2015 Apr TI - Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats. PG - 124-30 LID - 10.1111/jsr.12242 [doi] AB - Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation. CI - (c) 2014 European Sleep Research Society. FAU - Ventskovska, Olena AU - Ventskovska O AD - Institute of Biomedicine, University of Helsinki, Helsinki, Finland; Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkov, Ukraine. FAU - Porkka-Heiskanen, Tarja AU - Porkka-Heiskanen T FAU - Karpova, Nina N AU - Karpova NN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140915 PL - England TA - J Sleep Res JT - Journal of sleep research JID - 9214441 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Basal Forebrain/*metabolism MH - Brain-Derived Neurotrophic Factor/*genetics MH - Circadian Rhythm/*genetics MH - *DNA Methylation MH - Epigenesis, Genetic MH - Frontal Lobe/*metabolism MH - Male MH - Neuronal Plasticity MH - Promoter Regions, Genetic/genetics MH - RNA, Messenger/analysis/genetics MH - Rats MH - Sleep/*genetics MH - Sleep Deprivation/*genetics/physiopathology MH - Time Factors MH - Wakefulness/*genetics OTO - NOTNLM OT - Bdnf exon OT - circadian OT - diurnal OT - methylated DNA immunoprecipitation OT - sleep homeostasis EDAT- 2014/09/17 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/09/17 06:00 PHST- 2014/05/12 00:00 [received] PHST- 2014/08/10 00:00 [accepted] PHST- 2014/09/17 06:00 [entrez] PHST- 2014/09/17 06:00 [pubmed] PHST- 2015/05/15 06:00 [medline] AID - 10.1111/jsr.12242 [doi] PST - ppublish SO - J Sleep Res. 2015 Apr;24(2):124-30. doi: 10.1111/jsr.12242. Epub 2014 Sep 15.