2006 - Anitbodies kill brain cells
Study links disease, emotional state
BY JAMIE TALAN
STAFF WRITER
January 10, 2006
Antibodies that the body makes to fight lupus can leak into the brain and may alter behavior, according to a new study of mice bred as an animal model of the autoimmune disease.
The study raises the question of whether these antibodies could be having similar effects in humans with lupus.
Humans have a blood-brain barrier designed to protect the brain from harmful substances in the bloodstream, but it can be breached.
Dr. Betty Diamond and colleagues at Columbia University Medical Center in Manhattan took animals with the lupus antibody in the bloodstream and used a substance (the stress hormone epinephrine) to temporarily open the blood-brain barrier.
Once inside the brain, the antibody started killing neurons in the amygdala, a brain region governing fear and other emotional responses.
The animals then no longer responded to the threat of an electrical shock.
"This is a fantastic advance that may change the way we think about how disease affects behavior and emotion," said Dr. Kevin Tracey, director and chief executive at the Feinstein Institute for Medical Research, part of the North Shore-Long Island Jewish Health System.
"It tells us that this antibody, which is associated with lupus, may be able to get into the brain and control how people think, feel and act." Tracey was not involved in the research.
The study was published last week in the Proceedings of the National Academy of Sciences.
The finding may help explain many of the psychiatric complaints of lupus patients, whose autoimmune condition targets tissues of many organs throughout the body.
Though lupus symptoms vary, psychosis, depression, seizures, headache, dizziness and memory disturbances are common.
Diamond and colleagues studying the disease's anti-DNA antibodies have found that they leak into the brain and bind to neurons that make a brain chemical called glutamate.
Though glutamate is essential for normal brain function, too much can be toxic to these brain cells.
In a subsequent experiment, Diamond used an Alzheimer's drug (memantine) that blocks glutamate and found that it prevented the neuronal death in the brain's fear center. The researchers have identified a peptide, a small molecule, that in the lab seems to protect these neurons from the antibodies.
Many things can temporarily open the blood-brain barrier, including smoking, hypertension and inflammation. Diamond's study suggests that epinephrine, a hormone triggered by stress, also can temporarily open the blood-brain barrier.
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