December 22, 1998
La Jolla, CA – Forget something lately? If so, perhaps you should try an extra helping of sweet potatoes or other vitamin A-rich foods on the holiday table.
Researchers at the Salk Institute for Biological Studies have discovered that vitamin A promotes learning, and they have provided the first evidence that the vitamin affects brain cell activity in a region linked to learning and memory.
The results, published in the current issue of the journal Neuron, underscores concerns about the consequences of vitamin A deficiency, estimated to affect 190 million children worldwide.
“We have long known that vitamin A is needed for proper development of the nervous system in a growing embryo,” said Ronald Evans, Salk professor and senior author of the study. “This is the first evidence that vitamin A is needed for brain function during life.”
Vitamin A has a variety of beneficial properties?in particular, its role in vision has been appreciated for many years. The vitamin exerts these effects by attaching to specific molecules called receptors that reside within cells, detect the vitamin’s presence, and help it to control complex genetic networks.
There is a family of receptors for vitamin A, and different combinations of family members are active in different tissues in the body. Investigators in Evans’ laboratory noticed that two of these receptors, named RARbeta and RXRgamma, were active in only a small number of cells, “and some of those cells happened to be in parts of the brain that had been implicated as important in learning and memory,” explained Ming-Yi Chiang, first author on the study. “This finding prompted us to think that these two receptors might affect the ability to learn.”
Chiang and her colleagues made “knockout” mice that lacked genes for the two brain-specific receptors. The brains of the mice appeared to be normal in structure, indicating that the lack of the receptors did not affect embryonic development of the brain. The mice developed normally but performed much more poorly than ordinary mice in standard intelligence tests.
“Since the wiring in these mice appeared to be normal, we decided to look at whether the cells were working properly,” said Evans.
To do this, they teamed up with investigators in two other Salk laboratories, headed by Professors Fred Gage and Charles Stevens. The Stevens group examined the ability of brain cells from the “knockout” mice to undergo a process widely believed to be critical for learning.
During learning, brain cells communicate with one another across small gaps called synapses. When an electrical impulse has traveled the length of a brain cell and reached the tip, a chemical messenger shoots across the gap and triggers an impulse in an adjacent cell. “Like runners in a relay,” said Stevens, “pathways of brain cells generate our thoughts and memories.”
But in a race, not all batons are passed equally well, and communication across synapses can also vary. In fact, learning is accompanied by well-defined changes in the efficiency with which messages cross synapses. “It’s as if the brain fine-tunes those pathways involved in learning a particular task or fact,” says Stevens.
The investigators found that brain cells from the hippocampus of the knockout mice, the brain region known to be important in learning and memory, do not have this ability to modify their synapses. “Therefore, we have an unexpected link between a common but essential nutrient, the capacity to learn, and the cellular circuits in the brain that control learning,” says Evans. “Together, the evidence suggests that vitamin A is a type of molecular key that unlocks one of the most powerful functions of the human brain.”
Salk co-investigators include Dinah Misner, Gerd Kemperman, Thomas Schikorski, and Professor Fred Gage. Evans and Stevens are Howard Hughes Medical Institute investigators. Evans is also March of Dimes Chair in Molecular Developmental Biology. The study was done in collaboration with Vincent Giguére at McGill University in Montreal and Henry M. Sucov at the University of Southern California School of Medicine.
The work was supported by the G. Harold and Leila Y. Mathers Foundation, the Robert Glenn Rapp Foundation and the National Institutes of Health.
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, MD, with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.