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MIT: Magnesium may reverse middle-age memory loss

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Magnesium helps build bones, make proteins, release energy stored in muscles and regulate body temperature. In the cover story of the Dec. 2 issue of Neuron, MIT researchers report a possible new role for magnesium: helping maintain memory function in middle age and beyond.

The adult daily nutritional requirement for magnesium, a trace mineral found in foods such as dark green, leafy vegetables, is around 400 mg a day. But studies show that as many as half of all Americans do not consume enough magnesium. Magnesium deficits have been tied to allergies, asthma, attention deficit disorder, anxiety, heart disease, muscle cramps and other conditions.

Associate Professor Guosong Liu and postdoctoral associate Inna Slutsky at MIT's Picower Center for Learning and Memory found that magnesium helps regulate a key brain receptor important for learning and memory. Their work provides evidence that a magnesium deficit may lead to decreased memory and learning ability, while an abundance of magnesium may improve cognitive function.

"Our study shows... maintaining proper magnesium in the cerebrospinal fluid is essential for maintaining the plasticity of synapses," the authors wrote. "Since it is estimated that the majority of American adults consume less than the estimated average requirement of magnesium, it is possible that such a deficit may have detrimental effects... resulting in potential declines in memory function."

Plasticity, or the ability to change, is key to the brain's ability to learn and remember. Synapses, the connections among brain cells, undergo physical changes in response to brain activity. While the mechanisms underlying these changes remain elusive, it is known that synapses are less plastic in the aging or diseased brain. Loss of plasticity in the hippocampus, where short-term memories are stored, causes the forgetfulness common in older people.

"The important issue is how the plasticity of synapses is regulated physiologically," said Liu, who has appointments in MIT's Department of Biology and Department of Brain and Cognitive Sciences. Working with Slutsky, graduate student Safa Sadeghpour and technician Bing Li, Liu identified a key principle that predicts which chemicals can enhance plasticity.

This finding is akin to the difference between hearing music on an old radio or a high-fidelity stereo. Synapses, like speakers, have a level of background noise that can get in the way of transmitting their signal from one neuron to another. Just as our ears become more sensitive to nuances in music played on a top-of-the-line music system, synapses become more plastic when background noise is reduced.

Armed with this new understanding, the researchers then identified magnesium's importance in synaptic function.

Magnesium is the gatekeeper for the NMDA receptor, which receives signals from an important excitatory neurotransmitter involved in synaptic plasticity. Magnesium helps the receptor open up for meaningful input and shut down to background noise. "As predicted by our theory, increasing the concentration of magnesium and reducing the background level of noise led to the largest increases of plasticity ever reported in scientific literature," Liu said.

The researchers have identified and are now studying several families of drugs that may restore learning and memory in animals. Most important, Liu said, "This new theory may help create strategies to prevent aging-induced loss of synaptic plasticity."

This work was supported by the RIKEN-MIT Neuroscience Center and the National Institutes of Health.

A version of this article appeared in MIT Tech Talk on December 8, 2004 (download PDF).

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