Progressive dendritic pathology in cynomolgus macaques infected with simian immunodeficiency virus

Neuronal pathology in acquired immunodeficiency syndrome (AIDS) is of inter est in relation to cognitive impairment in AIDS patients and from the broad er perspective of the pathogenesis of neurodegeneration. Cortical dendritic spine loss has been described in patients with AIDS and the aim of this st udy was to test the hypothesis that similar pathology is present in cynomol gus macaques infected with simian immunodeficiency virus (SIV). These anima ls develop an AIDS-like illness, but multinucleated giant cell encephalitis is not a feature and CNS virus load is found to be very low. Four animals infected for 2.5-3 months and four infected for 2-3 years were compared wit h four controls. The Golgi-Cox technique was employed to demonstrate dendri tic morphology in the frontal cortex and the diameter of apical dendrites, dendritic spine density and dendritic spine lengths were measured in layer V pyramidal cells. Immunohistochemistry for micotubule-associated protein-2 (MAP-2), MHC class II and glial fibrillary acidic protein (GFAP) was also:p erformed. Infected animals there was progressive spine loss and atrophy of remaining spines with loss of MAP-2 immunoreactivity at late time points. N o parallel increase in GFAP immunostaining or MHC-class II expression in mi croglial cells was seen. We conclude that progressive neuronal dendritic pa thology is a feature of SIVmac251 infection of cynomolgus macaques and is a pparent relatively early in disease. Furthermore, dendritic abnormalities o ccur in the absence of either multinucleated giant cell pathology or substa ntial CNS virus load.