Differential epigenetic programming of hippocampal steroidogenesis by cognitive stimulation and voluntary exercise

ROSSETTI, M.F; LAZZARINO, G.P.; SCHUMACHER, R.; VARAYOUD, J; CANESINI, G.; RAMOS, J.G

Daegu

Congreso; The 10th IBRO World Congress of Neuroscience; 2019

Environmental enrichment (EE) promotes neuronal protectionthrough various mechanisms of action. Neurosteroids are steroidhormones synthesized de novo from cholesterol or steroidal pre-cursors in various brain regions and they have positive effects onneurogenesis, synaptic connectivity and cognitive performance.We analyzed the effects of a short-term EE on the mRNA expressionand DNA methylation of steroidogenic enzymes in the hippocam-pus. For that, young (90-day-old) and aged (360-day-old) femaleWistar rats were exposed to cognitive stimulation (CS) or vol-untary exercise (VE) during 10 days and compared to animalshoused under standard conditions (SC). CS was provided by anassortment of objects that included plastic tubes and toys; forVE, rodent dwellings were provided. In young animals, both CSand VE increased the mRNA expression of P450(17) and 3-HSDenzymes and decreased the expression of P450arom. In addi-tion, CS increased the transcription of 5R-1. Interestingly, VEupregulated P450(11)-2 gene expression in both young and agedanimals compared to SC. These results suggested that aged ratswould require a more prolonged stimulus than do young adultanimals to observe a similar effect. We observed hypomethyla-tion at the 5R-1 gene (site d) produced by CS and at the 5R-1(site a) and 3-HSD promoters produced by VE, in young rats.The fact that two different sites of the CpG Island 5R-1 pro-moter altered their methylation patterns depending on the EE,suggest that these sites could be potentially regulatory stimulus-specific sites. In aged rats, CS and VE decreased methylationlevels at a cis-actingelement Ad1 of the P450(11)-2 pro-moter. Altogether, these results proposed that sensory and motorenrichment differentially regulate the transcription of steroido-genic enzymes through epigenetic mechanisms associated withdifferential promoter methylation in the young and aged rathippocampus.