Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated.
Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immunodeficiency syndrome (murine AIDS) and an encephalopathy characterized by impaired spatial learning and memory. Because platelet-activating factor (PAF) has been implicated in the pathogenesis of HIV-associated dementia complex, brain PAF levels were measured in LP-BM5 MuLV-infected mice. PAF levels in cerebral cortex and hippocampus were significantly increased at 6 and 12 weeks after LP-BM5 MuLV inoculation, whereas significant increases in striatal and cerebellar PAF levels were observed only at 12 weeks after inoculation. Administration of the NMDA antagonist MK-801 significantly reduced the increased PAF levels in the cerebral cortex and hippocampus of LP-BM5 MuLV-infected mice. These results indicate that the LP-BM5 MuLV-induced increases in brain PAF levels are the results of NMDA receptor activation and are consistent with the hypothesis that elevated CNS PAF levels contribute to the behavioral deficits observed in LP-BM5 MuLV-infected mice.
Nishida
K
K
Section on Analytical Biochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Markey
S P
SP
Kustova
Y
Y
Morse
H C
HC
Skolnick
P
P
Basile
A S
AS
Sei
Y
Y
D015526:AIDS Dementia Complex / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D010972:Platelet Activating Factor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate