Enhanced Excitotoxicity in Primary Feline Neural Cultures Exposed to Feline Immunodeficiency Virus (FIV).

Abstract

The ability of feline immunodeficiency virus (FIV) to induce neurodegenerative changes in vitro similar to those due to HIV was examined as a potential model to examine the mechanisms underlying AIDS dementia. Primary cultures of feline neural tissue (neurons, astrocytes and microglia) were established from E40-E57 fetal cat cortex and challenged by inoculation with the NCSU₁ strain of FIV. Proviral FIV was detected in the cultures and correlated with the presence of microglia. No direct toxicity of FIV was seen. Stimulation of FIV-inoculated cortical cultures with 20 uM glutamate resulted in a greatly enhanced acute swelling response in approximately 14-24% of the neurons and an increase in the number of dead cells after 24 h relative to control cultures. The enhanced responses were due to an increase in the sensitivity of the cells to glutamate and were dependent on the presence of a soluble factor in the medium. The similarity of the indirect excitoxic effects of FIV to current models of HIV-gp120 neurotoxicity and the versatility of the in vitro cultures, indicate that FIV should provide a valuable model for the investigation of the mechanisms of neurodegeneration in AIDS dementia.