Nitric oxide synthase in reactive astrocytes adjacent to beta-amyloid plaques.
This study provides the first evidence that nitric oxide is released by astrocytes surrounding beta-amyloid plaques. Nitric oxide is involved in many neuropathological conditions and can have either a neuroprotective or a neurotoxic function depending on its concentration and the redox state of the tissue. It is produced by the enzyme nitric oxide synthase, which can be located by a simple histochemical technique for demonstrating NADPH diaphorase. Using this method we examined tissue from 10 brains where there were varying numbers of beta-amyloid plaques in the cerebral cortex. In the 6 brains with moderate or high densities of plaques, primitive and cored plaques were associated with between 1 and 10 reactive astrocytes that contained NADPH diaphorase or were immunoreactive for the inducible form of nitric oxide synthase. In the 4 brains which had only low densities of plaques, the plaques were not associated with diaphorase-containing astrocytes. The percentage of plaques associated with 1 or more NADPH diaphorase-containing astrocyte varied between 1 and 21% and was correlated with the density of plaques. Astrocytes were the only form of NADPH diaphorase-positive glial cell associated with the plaques. There was no evidence of any nitric oxide synthase occurring in microglia.
Wallace
M N
MN
Department of Biomedical Sciences, University of Aberdeen, Scotland.
Geddes
J G
JG
Farquhar
D A
DA
Masson
M R
MR
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001253:Astrocytes / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology*; D016207:Cytokines / Q000502:physiology; D015161:Dementia, Multi-Infarct / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D010084:Oxidation-Reduction; D016037:Single-Blind Method
D016229:Amyloid beta-Peptides; D016207:Cytokines; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase