Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats.
PLoS ONE. 2008-10-22; 3(10): e3487
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1. PLoS One. 2008;3(10):e3487. doi: 10.1371/journal.pone.0003487. Epub 2008 Oct 22.
Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory
deficit in vitamin A deprived rats.
Bonnet E(1), Touyarot K, Alfos S, Pallet V, Higueret P, Abrous DN.
(1)Nutrition & Neurosciences laboratory, University of Bordeaux 1, Talence,
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
PMID: 18941534 [Indexed for MEDLINE]