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

Simposio; II Simposio Franco-Argentino de Neurociencias; 2012

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 neurotrophic genes and 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), vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor 1 (HIF-1). The results showed that sensory stimulation increased the expression of Syp, Ppp1, VEGF-A, iNOSand nNOS inyoung animals (JAE vs 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 3 alpha-HSD and P450c17 (JAE vs JAS, p <0.05). However, this effect could not be seen in older animals (MAE vsMAS, p> 0.05). In conclusion, the neurotrophic effect of an enriched environment exposure was observed in young animals that showed an activation of neurotrophic genes associated with the formation of new synapses. These animals increased the expression of some enzymes involved in the synthesis of progestins and androgens in the hippocampus. The results support our hypothesis that the older females are unable to activate the synthesis of neurosteroids causing the decrease in neuronal plasticityassociated with age.