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Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11714-9. Epub 2001 Sep 11.

Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity.

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  • 1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, Howard Hughes Medical Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.


Despite its long history, the central effects of progressive depletion of vitamin A in adult mice has not been previously described. An examination of vitamin-deprived animals revealed a progressive and ultimately profound impairment of hippocampal CA1 long-term potentiation and a virtual abolishment of long-term depression. Importantly, these losses are fully reversible by dietary vitamin A replenishment in vivo or direct application of all trans-retinoic acid to acute hippocampal slices. We find retinoid responsive transgenes to be highly active in the hippocampus, and by using dissected explants, we show the hippocampus to be a site of robust synthesis of bioactive retinoids. In aggregate, these results demonstrate that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain, and suggest that key genes required for long-term potentiation and long-term depression are retinoid dependent. These data suggest a major mental consequence for the hundreds of millions of adults and children who are vitamin A deficient.

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