A dysfunction of
retinoid hippocampal signaling pathway has been involved in the appearance of affective and
cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of
vitamin A deficiency (VAD) on neurogenesis and memory and the ability of
retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult
retinoid-deficient rats were generated by a
vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis,
retinoid target genes such as
neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to
memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of
retinoid-mediated molecular events, such as the expression of the
neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of
vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function.