Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) tat protein causes inflammation, gliosis, apoptosis, and ventricular enlargement.
To determine the role of the Tat protein of the human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was injected intraventricularly as a single or repeated dose into male Sprague-Dawley rats. Histopathological evaluation showed an initial infiltration of neutrophils one day after Tat injection, followed by macrophages and lymphocytes by 7 days. Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular enlargement 7 days following the last injection. Nuclear magnetic resonance spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that the transient extracellular exposure of the central nervous system to Tat protein of HIV can cause a cascade of events leading to the influx of inflammatory cells, glial cell activation, and neurotoxicity.
Jones
M
M
Department of Microbiology and Immunology, University of Kentucky, Lexington, USA.
Olafson
K
K
Del Bigio
M R
MR
Peeling
J
J
Nath
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001253:Astrocytes / Q000502:physiology; D001479:Basal Ganglia / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001710:Biotin; D002540:Cerebral Cortex / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002552:Cerebral Ventricles / Q000276:immunology / Q000473:pathology*; D018792:Encephalitis, Viral / Q000276:immunology / Q000473:pathology; D004805:Ependyma / Q000473:pathology; D015696:Gene Products, tat / Q000494:pharmacology*; D005911:Gliosis / Q000473:pathology* / Q000821:virology; D018698:Glutamic Acid / Q000032:analysis; D015497:HIV-1; D006624:Hippocampus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007276:Injections, Intraventricular; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009504:Neutrophils; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013194:Staining and Labeling; D005680:gamma-Aminobutyric Acid / Q000032:analysis; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001710:Biotin; C000179:N-acetylaspartate