Astrocytes expressing Nef promote apoptosis and SMAD signaling in Neurons

Abstract

HIV is known to infect cells in the brain causing neurological impairments. Damage ranges from mild (HAND) to severe (HAD). We found learning impairment in rats infused with astrocytes expressing Nef. Histological studies performed on the brain tissues showed loss of neurons near the infusion site as well as evidence for TGFB signaling. We set up in vitro experiments to test for relationships between astrocytic Nef, TGFB signaling and neuron loss. We propose this loss is due to an apoptotic response of the neurons to the astrocytes expressing Nef. We exposed neuronal cells to astrocytes expressing Nef or GFP. Annexin V staining was used to measure apoptosis and a reporter assay measured SMAD activity by TGFB signaling. Results suggest that astrocytic Nef expression causes neuronal apoptosis. These neurons also show an increase in SMAD reporter activity. These studies suggest that loss of neurons may have been due to apoptosis caused by astrocytic Nef expression. These studies are relevant to understanding the high prevalence of HAND among patients receiving antiretroviral treatment.Supported by STEP‐UP Program, DA026722, RR003050/MD007579, GM09695 and 5G12RR003050/8G12MD007579.