Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats

PLoS One. 2008;3(10):e3487. doi: 10.1371/journal.pone.0003487. Epub 2008 Oct 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Neurogenesis / drug effects*
  • Rats
  • Receptor, trkA / genetics
  • Regeneration
  • Treatment Outcome
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use*
  • Up-Regulation
  • Vitamin A Deficiency / complications*
  • Vitamin A Deficiency / drug therapy


  • Tretinoin
  • Receptor, trkA