Ventskovska, Olena;
Porkka‐Heiskanen, Tarja;
Karpova, Nina N.
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
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Media type:
E-Article
Title:
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
Contributor:
Ventskovska, Olena;
Porkka‐Heiskanen, Tarja;
Karpova, Nina N.
Published:
Wiley, 2015
Published in:
Journal of Sleep Research, 24 (2015) 2, Seite 124-130
Description:
<jats:title>Summary</jats:title><jats:p>Brain‐derived neurotrophic factor (<jats:styled-content style="fixed-case">B</jats:styled-content>dnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control <jats:styled-content style="fixed-case">B</jats:styled-content>dnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of <jats:styled-content style="fixed-case">B</jats:styled-content>dnf by sleep or sleep deprivation. Here we investigated whether 5‐methylcytosine (5m<jats:styled-content style="fixed-case">C</jats:styled-content>) <jats:styled-content style="fixed-case">DNA</jats:styled-content> modification at <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> promoters p1, p4 and p9 influences <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf1</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">B</jats:styled-content>dnf4</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf9a</jats:italic> expression during the normal inactive phase or after sleep deprivation (<jats:styled-content style="fixed-case">SD</jats:styled-content>) (3, 6 and 12 h, end‐times being <jats:styled-content style="fixed-case">ZT</jats:styled-content>3, <jats:styled-content style="fixed-case">ZT</jats:styled-content>6 and <jats:styled-content style="fixed-case">ZT</jats:styled-content>12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> expression: <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf1</jats:italic> expression was highest at <jats:styled-content style="fixed-case">ZT</jats:styled-content>6 and <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf4</jats:italic> lowest at <jats:styled-content style="fixed-case">ZT</jats:styled-content>12. Such variation was not observed in the basal forebrain. Also <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> p1 and p9 methylation levels differed only in the cortex, while <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf1</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf4</jats:italic> with the similar pattern for <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf9a</jats:italic> in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5m<jats:styled-content style="fixed-case">C</jats:styled-content> levels at the cortical <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> p4 and p9. Regression analysis between the 5m<jats:styled-content style="fixed-case">C</jats:styled-content> promoter levels and the corresponding <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> transcript expression revealed significant negative correlations for the basal forebrain <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf1</jats:italic> and cortical <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf9a</jats:italic> transcripts in only non‐deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>dnf</jats:italic> transcription during the light phase of undisturbed sleep–wake cycle but not after <jats:styled-content style="fixed-case">SD</jats:styled-content> is regulated at least partially by brain site‐specific <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation.</jats:p>