Lithium: A Weapon Against Huntington's?

MIAMI--An old drug may perform a new neurological trick. Lithium, used for 50 years to treat manic depression, also protects against a rat version of Huntington's disease, researchers reported here this week at the Society for Neuroscience's annual meeting.

Huntington's disease, a deadly inherited condition with no known cure or reliable treatment, causes its victims to twitch and flail uncontrollably. The reason for this is that medium spiny neurons, in a brain area called the striatum that is involved in motor control, get overexcited by high levels of the neurotransmitter glutamate. Like an electrical fuse fried by too much juice, the brain neurons bombarded by glutamate get excited to death. Researchers can trigger Huntington's-like symptoms in rats by injecting quinoic acid into the striatum; the chemical kills the same neurons by the same mechanism.

Lithium is one of the more mysterious psychoactive drugs. It's still the treatment of choice for bipolar disorder, or manic-depression, but no one knows how it dampens severe mood swings. In the past few years, researchers led by neurobiologist De-Maw Chuang of the National Institutes of Health in Bethesda, Maryland, have discovered that lithium has another beneficial power: It protects neurons against over-excitation by glutamate. "The fact that lithium is neuroprotective came as a great surprise," says neurobiologist Richard Jope of the University of Alabama, Birmingham.

Chuang's team injected rats with doses of lithium, in proportion to what people with bipolar disorder might take, on one side of the rats' brains for either 1 day or 16 days. Then they injected the rats with quinoic acid. The brain regions pretreated with lithium lost only one-third as many cells as the unprotected neural tissue on the other side of the brain.

"This is great work," says Jope. The findings suggest that lithium specifically protects against the deterioration typical of Huntington's disease, he says, and "that's incredibly important." But testing lithium in Huntington's patients is years away.

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