Neuron loss and axon reorganization in the dentate gyrus of cats infected with the feline immunodeficiency virus

The pathophysiological bases of cognitive, motor, and behavioral abnormalit ies in patients infected with the human immunodeficiency virus (HIV-1) rema in largely unknown. To test the possibility that changes in hippocampal neu ronal structure may contribute to these neurologic abnormalities, we examin ed the brains of cats infected with the feline immunodeficiency virus (FIV) , an animal model of HIV-1 infection. We evaluated the dentate gyrus by usi ng Timm's staining to estimate the extent of granule cell axon reorganizati on and by using Nissl staining, immunocytochemistry, and the optical fracti onator method to estimate changes in the number of different neuronal subty pes. FIV-infected cats had abnormally high amounts of Timm's staining in th e inner molecular layer and granule cell layer and loss of Nissl-stained, s omatostatin-immunoreactive, and parvalbumin-immunoreactive neurons in the h ilus. An inverse correlation existed between hilar neuron numbers and exten t of aberrant Timm's staining. Increased Timm's staining and hilar neuron l oss occurred throughout the septotemporal axis of the hippocampus. This typ e of neuronal loss and synaptic reorganization may provide an anatomic basi s for some of the neurologic symptoms found in FIV-infected cats and HIV-in fected humans. (C) 1999 Wiley-Liss, Inc.