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Spontaneous sleep–wake cycle and sleep deprivation differently induce B dnf1, B dnf4 and B dnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats
Author(s) -
Ventskovska Olena,
PorkkaHeiskanen Tarja,
Karpova Ni.
Publication year - 2015
Publication title -
journal of sleep research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.297
H-Index - 117
eISSN - 1365-2869
pISSN - 0962-1105
DOI - 10.1111/jsr.12242
Subject(s) - sleep deprivation , basal forebrain , basal (medicine) , endocrinology , forebrain , epigenetics , medicine , rapid eye movement sleep , biology , sleep (system call) , privation , psychology , circadian rhythm , neuroscience , gene , genetics , electroencephalography , central nervous system , computer science , operating system , insulin
Summary Brain‐derived neurotrophic factor ( B dnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control B dnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of B dnf by sleep or sleep deprivation. Here we investigated whether 5‐methylcytosine (5m C ) DNA modification at B dnf promoters p1, p4 and p9 influences B dnf1 , B dnf4 and B dnf9a expression during the normal inactive phase or after sleep deprivation ( SD ) (3, 6 and 12 h, end‐times being ZT 3, ZT 6 and ZT 12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical B dnf expression: B dnf1 expression was highest at ZT 6 and B dnf4 lowest at ZT 12. Such variation was not observed in the basal forebrain. Also B dnf p1 and p9 methylation levels differed only in the cortex, while B dnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced B dnf1 and B dnf4 with the similar pattern for B dnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5m C levels at the cortical B dnf p4 and p9. Regression analysis between the 5m C promoter levels and the corresponding B dnf transcript expression revealed significant negative correlations for the basal forebrain B dnf1 and cortical B dnf9a transcripts in only non‐deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that B dnf 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.