Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus.

ROSSETTI MF; VARAYOUD J; MORENO PIOVANO G; LUQUE EH; RAMOS JG

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2015

0303-7207

Aging is associated with a decline in cognitive functions; in contrast neurosteroids synthesis promotes neuroprotective and neurotrophic mechanisms. Here, we analyzed the effects of aging and enriched environment on the mRNA expression and DNA methylation state of hippocampal steroidogenic enzymes. The effects of aging were evaluated comparing the mRNA expression of steroidogenic enzymes in young adult (90 days old) and middle-aged (345 days old) Wistar female rats. To elucidate the effects of environmental enrichment a subgroup of middle-aged rats were exposed during 105 days to sensory and social stimulation;and compared to rats housed under standard laboratory conditions. Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of P450scc (cytochrome P450 side chain cleavage), 3α-HSD (3α-hydroxysteroid dehydrogenase) and 5α-reductase-1. Interestingly, middle-aged rats exposed to environmental enrichment reduced the age-related decrease of the mRNA levels of 5α-reductase-1, 3α-HSD and P450(17α) (cytochrome P450 17α-hydroxylase/c17,20-lyase) and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuates the age-related decline in the mRNA expression of steroidogenic enzymes in the rat hippocampus. Epigenetic mechanisms associated with differential promoter methylation could be, at least in part, implicated.