Regional changes in constitutive, but not inducible NOS expression in the brains of mice infected with the LP-BM5 leukemia virus.
Potential neurotoxins such as nitric oxide have been implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) dementia complex. The LP-BM5 murine leukemia-infected mice, which develop immunological and cognitive deficits reminiscent of human HIV-1 infection, were employed to investigate the changes in brain constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) expression. Cerebellar and striatal cNOS enzymatic activity increased approximately 70% as early as 2 weeks after infection, declining to control levels by 12-16 weeks. In contrast, cNOS protein expression in the striatum and cerebellum was decreased 30% at 4 weeks, declining to 50% of control levels by 16 weeks post-infection. Staining intensity for cNOS, but not neuron number was reduced in the cerebral cortex, striatum, ventromedial hypothalamic nucleus and amygdala. Although iNOS protein expression was elevated in splenic monocytes, neither iNOS activity, mRNA nor protein was detected in the brains of mice 12 weeks after infection. These results indicate that neurons decrease cNOS protein expression to compensate for chronic cNOS activation, probably resulting from glutamatergic stimulation. The cNOS activation is contemporaneous with microglial activation in LP-BM5-infected mice, and precedes the development of cognitive deficits. Moreover, the lack of iNOS induction in either infected macrophages or glial elements suggests that iNOS is not necessary for the development of these cognitive deficits.
Li
Y
Y
Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Kustova
Y
Y
Sei
Y
Y
Basile
A S
AS
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D007150:Immunohistochemistry; D009052:Leukemia Virus, Murine; D007942:Leukemia, Experimental / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012192:Retroviridae Infections / Q000201:enzymology*; D013997:Time Factors; D014018:Tissue Distribution; D014412:Tumor Virus Infections / Q000201:enzymology*
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase