Cytosine demethylation in the tyrosine hydroxylase gene promoter in hypothalamus cells of rat brain under the action of 2-aminoadamantane compound Ladasten

Abstract

In our previous study of mechanisms of pharmacological activity of a derivative of 2-aminoadamantane, Ladasten, we have shown more than a twofold increase in the mRNA level of the tyrosine hydroxylase (TH) gene in the rat brain hypothalamus 1.5–2.0 h after a single administration of this substance. In the present study, we employed the bisulfate sequencing technique to detect changes of GpG islands methylation status in the TH gene 5′-flanking region (−650)−(+84) in hypothalamus cells of control and experimental rats after a single exposure to Ladasten. Ladasten was shown to increase frequency of cytosine demethylation in binding sites of some transcription factors or in neighboring motifs. It is suggested that the Ladasten-induced increase of TH gene transcriptional activity in rat hypothalamus is associated with cytosine demethylation in CpG islands in some regulatory gene elements.