Magnesium enhances learning and memory

New research finds that an increase in brain magnesium improves learning and memory in young and old rats. The study, published by Cell Press in the January 28th issue of the journal Neuron, suggests that increasing magnesium intake may be a valid strategy to enhance cognitive abilities and supports speculation that inadequate levels of magnesium impair cognitive function, leading to faster deterioration of memory in aging humans.

Diet can have a significant impact on cognitive capacity. Identification of dietary factors which have a positive influence on synapses, the sites of communication between neurons, might help to enhance learning and memory and prevent their decline with age and disease. Professor Guosong Liu, Director of the Center for Learning and Memory at Tsinghua University in Beijing, China, led a study examining whether increased levels of one such dietary supplement, magnesium, boosts brain power.

Magnesium, an essential element, is found in dark, leafy vegetables such as spinach and in some fruits. Those who get less than 400 milligrams daily are at risk for allergies, asthma and heart disease, among other conditions. In 2004, Guosong Liu and colleagues at MIT discovered that magnesium might have a positive influence on learning and memory. They followed up by developing a new magnesium compound — magnesium-L-threonate (MgT) —that is more effective than conventional oral supplements at boosting magnesium in the brain, and tested it on rats.

"We found that elevation of brain magnesium led to significant enhancement of spatial and associative memory in both young and aged rats," said Liu, now director of the Center for Learning and Memory at Tsinghua University. "If MgT is shown to be safe and effective in humans, these results may have a significant impact on public health." Liu is cofounder of Magceutics, a California-based company developing drugs for prevention and treatment of age-dependent memory decline and Alzheimer's disease.

"Half the population of the industrialized countries has a magnesium deficit, which increases with aging. If normal or even higher levels of magnesium can be maintained, we may be able to significantly slow age-related loss of cognitive function and perhaps prevent or treat diseases that affect cognitive function," Liu said.

HOW THEY DID IT: To understand the molecular mechanisms underlying this MgT-induced memory enhancement, the researchers studied the changes induced in functional and structural properties of synapses. They found that in young and aged rats, MgT increased plasticity among synapses, the connections among neurons, and boosted the density of synapses in the hippocampus, a critical brain region for learning and memory.

Susumu Tonegawa at MIT's Picower Institute for Learning and Memory helped carry out the initial behavioral experiments that showed that magnesium boosted memory in aged rats. Min Zhou's laboratory at the University of Toronto helped demonstrate the enhancement of synaptic plasticity in magnesium-treated rats.

"Magnesium is essential for the proper functioning of many tissues in the body, including the brain and, in an earlier study, we demonstrated that magnesium promoted synaptic plasticity in cultured brain cells," explains Dr. Liu. "Therefore it was tempting to take our studies a step further and investigate whether an increase in brain magnesium levels enhanced cognitive function in animals."

Because it is difficult to boost brain magnesium levels with traditional oral supplements, Dr. Liu and colleagues developed a new magnesium compound, magnesium-L-threonate (MgT) that could significantly increase magnesium in the brain via dietary supplementation. They used MgT to increase magnesium in rats of different ages and then looked for behavioral and cellular changes associated with memory.

"We found that increased brain magnesium enhanced many different forms of learning and memory in both young and aged rats," says Dr. Liu. A close examination of cellular changes associated with memory revealed an increase in the number of functional synapses, activation of key signaling molecules and an enhancement of short- and long-term synaptic processes that are crucial for learning and memory.

The authors note that the control rats in this study had a normal diet which is widely accepted to contain a sufficient amount of magnesium, and that the observed effects were due to elevation of magnesium to levels higher than provided by a normal diet.

"Our findings suggest that elevating brain magnesium content via increasing magnesium intake might be a useful new strategy to enhance cognitive abilities," explains Dr. Liu. "Moreover, half the population of industrialized countries has a magnesium deficit, which increases with aging. This may very well contribute to age-dependent memory decline; increasing magnesium intake might prevent or reduce such decline."


NEXT STEPS: This study not only highlights the importance of a diet with sufficient daily magnesium, but also suggests the usefulness of magnesium-based treatments for aging-associated memory decline, Tonegawa said. Clinical studies in Beijing are now investigating the relationship between body magnesium status and cognitive functions in older humans and Alzheimer's patients.