POISONS released by dying astrocytes- cells that normally nourish nerve cells and detoxify the brain-could solve the mystery of AIDS dementia.
One in five people with AIDS eventually develops dementia. The mystery is that HIV does not appear to infect nerve cells. Until now, the leading theory has been that AIDS dementia is due to the virus infecting microglia, a type of immune cell found only in the brain, which can produce toxic biochemicals such as quinolinic acid.
But a research team from Flinders University in Bedford Park, South Australia, and Johns Hopkins University in Baltimore recently discovered that HIV can also infect astrocytes, although it cannot multiply in them. The researchers wondered if this seemingly passive infection might still contribute to dementia.
They studied four brains from healthy people who had died in accidents, and 18 brains from people who had died from AIDS. The AIDS patients were divided into three groups: those who had never suffered dementia; "rapid dementers" who developed severe dementia over a period of months; and "slow dementers" who took several years to develop severe dementia.
The brains of those with dementia had significantly more astrocytes that had undergone apoptosis, or programmed cell death, compared with those of the controls and AIDS patients without dementia. This trend was especially marked among the rapid dementers. "They had significantly more apoptotic astrocytes than the slow dementers," says Kate Thompson, one of the researchers. "Maybe the rapiddementers are infected with a strain of virus that can infect astrocytes more easily," speculates Steve Wesselingh, another member of the Flinders team.
Once the astrocytes started dying off, the brain would begin to lose its main way of removing glutamate, an amino acid that at high concentrations can kill neurons. The excess glutamate would cause dementia.
Bruce Brew of the National Centre in HIV Research Epidemiology and Clinical Research in Sydney says that the next step will be to show that the death of astrocytes leads directly to the death or damage of neurons. The Flinders-Hopkins team also aims to find out exactly when the astrocytes become infected. "If they become infected immediately after contracting HIV there will not be much you can do," says Wesselingh. "If they don't become infected until later, it may be possible to prevent dementia by treating people with anti-HIV drugs from early in infection."
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