Lithium may protect neurons from radiation therapy

Drug may help prevent learning, memory deficits caused by treatment for brain tumors

Patients who undergo radiation for treatment of brain tumors may survive their cancer only to have lasting memory and learning deficiencies, the impact of which can be particularly devastating for children. Now, researchers at the Vanderbilt-Ingram Cancer Center have discovered that lithium, a drug commonly used to treat bipolar disorder and other mental illnesses, can protect the brain cells involved in learning and memory from radiation damage.

While the work has been conducted in cell culture and animal studies thus far, clinical trials are expected to be conducted soon to test whether the drug can protect humans from cognitive deficits as a result of cranial radiation therapy.

The researchers presented their work during the 46th annual meeting of the American Society for Therapeutic Radiology and Oncology, earlier this week in Atlanta. “In addition to killing cancer cells, radiation can cause cell death – apoptosis – in normal cells as well,” said Dennis Hallahan, M.D., professor and chair of Radiation Oncology at Vanderbilt University School of Medicine in Nashville, Tenn. “Particularly susceptible are neurons in the hippocampus, the part of the brain that plays a crucial role in learning and memory.”

Lithium is an inhibitor of a protein that causes apoptosis called glycogen synthase kinase 3 b. Studies suggest that it may protect neurons from a variety of cytotoxic insults, including observations that the incidence of Alzheimer’s disease – which leads to progressive and profound memory loss – is lower among patients who take lithium for mental illness, Hallahan said.

The researchers observed in animal models that a single radiation dose of 5 Gy caused a massive amount of apoptosis in the hippocampus but not in other areas of the brain.

However, treatment of a mouse hippocampus cell with lithium for a week prior to 3 Gy of radiation resulted in a 60 percent increase in cell survival; a week’s treatment with lithium prior to a radiation dose of 6 Gy resulted in a 70 percent increase in cell survival.

The researchers also observed animals in a maze to determine long-term effects on memory and learning, and found that the animals pre-treated with lithium performed better than those who did not receive lithium prior to radiation.

The team further noted that lithium did not appear to protect other types of brain cells studied, suggesting that its effects may be selective for neurons.

“Lithium may therefore provide a means of attenuating long-term cognitive deficits in patients treated with cranial irradiation,” the researchers said.