Nutritional vitamin A supplementation improves spatial memory in aged rats

Retinoic acid (RA), the active metabolite of vitamin A, has been reported to be involved in the control of hippocampal synaptic plasticity and in cognitive functions. Indeed, it has been shown that RA treatment can counteract the effects of vitamin A deficiency (VAD) on spatial memory deficits and on adult hippocampal neurogenesis disruption [1], a novel form of structural plasticity which has been involved in hippocampal-dependent learning processes. In aged subjects, the naturally occuring hypoactivity of the retinoid signaling pathway also induces spatial memory deficits [2].
In this study, we compared the effects of nutritional vitamin A supplementation (4 months) and RA treatment on spatial reference memory and on hippocampal neurogenesis in aged rats. We explored the possibility that nutritional vitamin A supplementation can be a successful strategy in preventing deterioration of hippocampal plasticity and aging-related decline in memory function. Spatial memory performances of the animals have been assessed in the Morris Water Maze. The different steps of hippocampal neurogenesis (proliferation, survival, differentiation) were followed by immunohistochemistry using specific markers. Moreover, we also investigated possible retinoid target genes involved in synaptic plasticity.
Our results show that nutritional vitamin A supplementation but not RA treatment prevents spatial memory deficits in aged rats. Moreover, vitamin A supplementation-induced improvement in spatial memory in aged subjects does not depend only upon hippocampal neurogenesis but also upon other hippocampal plasticity mechanisms.

1. Bonnet et al. 2008. PloS ONE 3,e3487.
2. Mingaud et al. 2008. J Neurosci 28,279-291.