It's long been known that people living with HIV experience a loss of white matter in their brains. As opposed to gray matter, which is composed of the cell bodies of neurons, white matter is made up of cells that produce myelin, a fatty substance that coats neurons, offering protection and helping them transmit signals efficiently. A reduction in white matter is associated with motor and cognitive impairment.
Earlier work by a team from Penn Dental Medicine and Children's Hospital of Philadelphia (CHOP) found that antiretroviral therapy (ART)—the lifesaving drugs that many with HIV use daily—can reduce white matter, but it wasn't clear how the virus itself contributed to this loss.
In a new study using both human and rodent cells, the team has determined how HIV prevents the myelin-making brain cells called oligodendrocytes from maturing, reducing white matter production. When the researchers applied a compound blocking to this process, the cells were once again able to mature. The work appears in the journal Glia.
"Even when people with HIV have their disease well-controlled by antiretrovirals, they still have the virus present in their bodies, so this study came out of our interest in understanding how HIV infection itself affects white matter," says Kelly Jordan-Sciutto, professor at Penn Dental Medicine and the study's co-senior author. "By understanding those mechanisms, we can take the next step to protect people with HIV from these impacts."
Jordan-Sciutto and Judith Grinspan, CHOP research scientist and Professor of Neurology at Penn Medicine, have been collaborating to elucidate how ART and HIV affect the brain. Their previous work on antiretrovirals had shown that commonly used drugs disrupted the function of oligodendrocytes, reducing myelin formation.
In the current study, they aimed to isolate the effect of HIV on this process by looking at human macrophages, one of the major cell types that HIV infects.
Ultimately, the researchers want to discern the effects of the virus from the drugs used to treat it in order to better evaluate the risks of each.
"When we put people on ART, it's important to understand the implications," says Jordan-Sciutto. "Antiretrovirals may prevent the establishment of a viral reservoir in the central nervous system, which would be wonderful, but we also know some drugs have unintended consequences, which may include altering white matter." Read more on the study >>