The impact of sensory and motor stimulation on the epigenetic control of steroidogenic-related genes in the rat hippocampus- Young Investigator Lecture

ROSSETTI, M.F

Encuentro; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias-SAN.; 2018

Environmental enrichment (EE) promotes neuronal protection through various mechanisms of action. Neurosteroids are steroid hormones synthesized de novo from cholesterol or steroidal precursors in various brain regions and they have positive effects on neurogenesis, synaptic connectivity and cognitive performance. We analyzed the effects of a short-term EE on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. For that, young (90-day-old) and aged (360-day-old) female Wistar rats were exposed to sensory (SE) or motor (ME) enrichment during 10 days and compared to animals housed under standard conditions (SC). SE was provided by an assortment of objects that included plastic tubes and toys; for ME, rodent dwellings were provided. In young animals, both SE and ME increased the mRNA expression of P450(17α) and 3α-HSD enzymes and decreased the expression of P450arom. In addition, SE increased the transcription of 5αR-1. Interestingly, ME upregulated P450(11β)-2 gene expression in both young and aged animals compared to SC. These results suggested that aged rats would require a more prolonged stimulus than do young adult animals to observe a similar effect. We observed hypomethylation at the 5αR-1 gene (site d) produced by SE and at the 5αR-1 (site a) and 3α-HSD promoters produced by ME, in young rats. The fact that two different sites of the CpG Island 5αR-1 promoter altered their methylation patterns depending on the EE, suggest that these sites could be potentially regulatory stimulus-specific sites. In aged rats, SE and ME decreased methylation levels at a cis-acting element Ad1 of the P450(11β)-2 promoter. Altogether, these results proposed that sensory and motor stimulation differentially regulate the transcription of steroidogenic enzymes through epigenetic mechanisms associated with differential promoter methylation in the young and aged rat hippocampus.