Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus.
Infection with human immunodeficiency virus-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS) in humans, causes a spectrum of neuropathology that includes alterations in behavior, changes in evoked potentials, and neuronal degeneration. In the simian immunodeficiency virus (SIV) model of HIV infection, affected monkeys show clinical symptoms and neurological complications that mimic those observed in human neuro-AIDS. To investigate the relationship between morphological correlates and neurophysiological deficits, unbiased stereology was used to assess total neuron number, volume, and neuronal density for all neurons in the globus pallidus (GP) and for dopamine (DA)-containing neurons in the substantia nigra (SN) in eight macaques inoculated with macrophage-tropic, neurovirulent SIV (SIVmac R71/17E), and five control animals. There was a significant difference between rapid progressors and controls for both neuron number (P < .01) and neuronal density (P < .05) in the GP, and for neuron number (P < .05) in the SN. Neuron loss ranged from 6% to 70% in the GP and from 10% to 50% in the SN. Neuropathological analyses confirmed neuroAIDS-like changes in brain, including microglial nodules, extensive perivascular cuffing and/or the presence of multinucleated giant cells, and alterations in neuronal morphology in the majority of the rapid progressors. By comparison, slow progressors showed little, if any, neuropathology. These neuropathological changes in SIV-infected monkeys indicate that neuron death and morphological alterations in the basal ganglia may contribute to the motor impairments reported in the SIV model and, by analogy, in the subset of patients afflicted with motor impairment in human neuro-AIDS.
Marcario
J K
JK
Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7185, USA. jmarcari@kumc.edu
Manaye
K F
KF
SantaCruz
K S
KS
Mouton
P R
PR
Berman
N E J
NE
Cheney
P D
PD
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology / Q000821:virology; D001921:Brain / Q000473:pathology* / Q000821:virology*; D002452:Cell Count; D018450:Disease Progression; D005917:Globus Pallidus / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D011597:Psychomotor Performance / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus; D013378:Substantia Nigra / Q000473:pathology / Q000821:virology