November 7, 2000

Vitamin A Deficiency Impairs Learning Functions In Reversible Manner

Salk News

Vitamin A Deficiency Impairs Learning Functions In Reversible Manner

La Jolla, CA – Removing Vitamin A from the diets of mice diminishes chemical changes in the brain considered the hallmarks of learning and memory. When vitamin A is added back to their diets, the impairment is reversed.

“These data indicate that vitamin A is necessary for optimal function in the hippocampus, which we know to be a main seat of learning,” said Salk researcher Sharoni Jacobs, who, with her colleagues, are presenting these results at the current Society for Neuroscience meeting in New Orleans, La.

Added Salk Professor Ronald M. Evans, senior author of the study: “The study indicates that the detrimental effects of vitamin A deprivation are remarkably reversible, which offers hope to the millions of children worldwide with vitamin A-deficient diets.”

In the study, genetically identical litter mates were given either a normal diet or one lacking vitamin A. At periodic intervals, the hippocampus regions of their brains were examined for LTP (long-term potentiation) and LTD (long-term depression), chemical measures of brain cell adaptability long believed to correlate with learning ability.

“At 15 weeks of age, the responses of vitamin A-deprived mice are reduced to about 50 percent normal. At longer time points, LTP is stable at 50 percent, but LTD drops to almost undetectable levels,” said Jacobs.

Adding vitamin A back to the diet for as little as two days restores brain responses to normal levels.

Normal function was also restored when isolated hippocampus tissue from the mice was bathed in vitamin A, indicating that the nutrient functions in the hippocampus directly, not in other parts of the brain that might influence the important learning region.

The current work builds on earlier studies from Evans’ laboratory, in which researchers found that mice born without receptors for vitamin A in the hippocampus lacked LTP ability and performed under par in standardized learning tests. Receptors are molecules within brain cells that detect and respond to the vitamin.

“What couldn’t be ruled out in those studies, however, was that vitamin A activity was needed during embryonic development to establish normal learning functions,” said Evans. “Now we’ve shown that removing vitamin A from fully-developed animals impairs learning pathways, and equally important, the effects are reversible.”

Salk co-authors include Dinah Misner, Yasushi Shimizu, Luigi De Luca and Professor Charles Stevens. The study, titled “A required role for vitamin A signaling in hippocampal long-term synaptic plasticity,” was supported by the National Institutes of Health and the Howard Hughes Medical Institute (HHMI). Evans and Stevens are Howard Hughes Medical Institute investigators.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

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