Brain cells We also examined the involvement of oligodendrocytes in patients with cognitive impairment associated with HIV infection. Previous findings from Jordan-Sciutto’s lab show that integrated stress responses are of other types.
This response integrates signals from four different signaling pathways, resulting in altered gene expression, protecting cells from stress and killing cells when stress is overwhelming. However, there was another mechanism that researchers suspected that they might be involved. This result suggests that glutamate secreted by infected macrophages causes progenitor cells to “stack” in the immature state. Sure enough, when researchers applied a compound that blunts glutamate levels in HIV, Infected macrophages Prior to transferring the growth medium to oligodendrocyte progenitor cells, the cells were able to mature into oligodendrocytes. The neurotransmitter glutamate is known to have neurotoxic effects at high levels. “Therefore, the next step was to figure out what is being secreted to bring this effect to oligodendrocytes.” “Virus-infected immune cells secrete harmful substances and usually target invading organisms, but they can also kill nearby cells, such as neurons, and prevent their differentiation,” Grinspan said. After that, myelin production also decreased. This treatment did not kill progenitor cells, but prevented maturation to oligodendrocytes. Oligodendrocytes Progenitor cells that mature into oligodendrocytes. To learn more about how this specifically affects white matter, researchers collected a growing fluid of HIV-infected macrophages and applied it to rats. Scientists have hypothesized that the effects of HIV on the brain were indirectly caused by the activity of these immune cells, because the virus does not infect neurons or oligodendrocytes. It started by examining one of the human macrophages. The study, led by Lindsey Ross, who recently received a PhD from the University of Pennsylvania’s Graduate School of Biomedicine Research Group and completed a postdoctoral fellow with Jordan Schut and Grinspan, found the major types of cells infected with HIV. Their previous studies of antiretroviral drugs have shown that commonly used drugs disrupt oligodendrocyte function and reduce myelin formation.Ĭurrent research aimed to isolate the effects of HIV on this process.
Jordan-Sciutto and Grinspan have been working together for several years to elucidate how ART and HIV affect the brain, especially oligodendrocytes, which is the focus of Grinspan’s research.
When researchers applied compounds that interfered with this process, the cells were able to mature again. In a new study using both humans and rodents cellThe research team elucidated the detailed mechanism and revealed how HIV prevents the maturation of myelin-producing brain cells called oligodendrocytes and adversely affects the production of white matter. White matter loss is associated with movement disorders and cognitive impairment.Ī previous study by a team from the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) found that antiretroviral therapy (ART), a life-saving drug that many HIV-infected people use daily, White matterHowever, it was not clear how the virus itself contributed to this loss. In contrast to the “gray matter,” which is made up of the cell bodies of neurons, the white matter is made up of a fatty substance called myelin that covers the neurons, providing protection and helping to transmit signals quickly and efficiently. It has long been known that people living with HIV experience loss of white matter in the brain. Researchers at Penn and CHOP have shown that HIV infection interferes with oligodendrocyte maturation and leads to a decrease in white matter in the brain. Confocal microscopic images show oligodendrocytes in cell culture, labeled with cell nuclei in blue and myelin proteins in red, green, and yellow.
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