Effects of acute ethanol exposure on class I HDACs family enzymes in wild-type and BDNF+/− mice

Abstract

BackgroundAlterations of brain-derived neurotrophic factor (BDNF) have been associated with the development of addiction to different drugs of abuse, including ethanol (EtOH). EtOH exposure activates the BDNF-signaling cascade in dorsal striatum, which in turn affects further EtOH intake. Different alcohol exposures have been widely demonstrated to modulate chromatin remodeling, affecting histone acetylation/deacetylation balance. Recently, class I histone deacetylases (HDACs) inhibition has been reported to modulate BDNF mRNA expression and to attenuate morphological and behavioral phenomena related to EtOH exposure. However, the role played by different HDAC isoforms in EtOH-induced plasticity is still unclear. MethodsWe investigated the effects induced by acute EtOH exposure on the protein levels of class I HDAC 1–3 isoforms of wild-type (WT) and BDNF heterozygous mice (BDNF+/−), in nuclear and cytoplasmic extracts of specific brain regions associated with EtOH addiction. ResultsNuclear HDAC 1–3 levels were markedly reduced after acute EtOH treatment in the caudate putamen (CPu) of WT mice only. Furthermore, CPu basal levels of nuclear HDAC isoforms were significantly lower in BDNF+/− mice compared to WT. With the exception of nuclear HDAC 3, no significant changes were observed after acute EtOH treatment in the prefrontal cortex (PFCx) of BDNF+/− and WT mice. In this area, the nuclear HDAC basal levels were significantly different between the two experimental groups. ConclusionsThese results provide details about EtOH effects on class I HDAC isoforms and strongly support a correlation between BDNF and class I HDACs, suggesting a possible influence of BNDF on these enzymes.