Changes in neurosteroid biosynthesis may contribute to the decline in neuronal plasticity associated with aged.

ROSSETTI MF; VARAYOUD J; MUÑOZ DE TORO M; LUQUE EH; RAMOS JG

Congreso; II Simposio Franco-Argentino de Neurociencias.; 2012

Sociedad Argentina de Neurociencias

Enriched environments improve spatial learning and memory function. In addition, some steroids synthesized in the brain have neurotrophic properties. The aim of this study was to evaluate if environmental enrichment modifies the expression of enzymes involved in neurosteroid biosynthesis in young and older female rats. Young (3 months old; JAE group) and older (15 months old; MAE group) Wistar female rats were exposed for 10 days to an enriched environment consisting of cages containing tunnels and toys of different shapes, sizes and colors, with a capacity for 8 animals. As controls we used young and older animals placedin standard cages (JAS and MAS respectively). After treatment hippocampus were removed and frozen in liquid nitrogen. Using real time RT-PCR, we analyzed the expression of synaptophysin (Syp), spinophilin (Ppp1), inducible and neuronal nitric oxide synthase (iNOS and nNOS respectively), endothelial growth factor (VEGF) and hypoxia-induciblefactor 1 (HIF-1). The results showed that sensory stimulation increased the expression of Syp, Ppp1, VEGF-A, iNOS and nNOS in young animals (JAEvs JAS, p <0.05). In contrast, environmental enrichment caused a reduction in Syp and Ppp1 expression in older rats (MAE vs MAS, p <0.05). Moreover, in young animals sensory stimulation increased the expression of 3alpha-HSD and P450c17 (JAE vsJAS, p <0.05). However, this effect could not be seen in older animals (MAEvs MAS, p> 0.05). In conclusion, the neurotrophic effect of an enriched environment exposure is observed only in young animals. These young females showed an activation of neurotrophic genes associated with the formation of new synapses and an increase in the expression of the enzymes involvedin the synthesis of progestins and androgens in the hippocampus. These results support our hypothesis that the older females are unable to activate the synthesis of neurosteroids causing the decrease in neuronalplasticity associated with age.