nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's disease.

Abstract

The immunocytochemical distribution of the neuronal form of nitric oxide synthase (nNOS) was compared with neuropathological changes and with cell death related DNA damage (as revealed by in situ end labeling, ISEL) in the hippocampal formation and entorhinal cortex of 12 age-matched control subjects and 12 Alzheimer's disease (AD) patients. Unlike controls, numerous nNOS-positive reactive astrocytes were found in AD patients around beta-amyloid plaques in CA1 and subiculum and at the places of clear and overt neuron loss, particularly in the entorhinal cortex layer II and CA4. This is the first evidence of nNOS-like immunoreactivity in reactive astrocytes in AD. In contrast to controls, in all but one AD subject, large numbers of ISEL-positive neuronal nuclei and microglial cells were found in the CA1 and CA4 regions and subiculum. Semiquantitative analysis showed that neuronal DNA fragmentation in AD match with the distribution of nNOS-expressing reactive astroglial cells in CA1 (r = 0.74, P < 0.01) and CA4 (r = 0.58, P < 0.05). A portion of the nNOS-positive CA2/CA3 pyramidal neurons was found to be spared even in the most affected hippocampi. A significant inverse correlation between nNOS expression and immunoreactivity to abnormally phosphorylated tau proteins (as revealed by AT8 monoclonal antibody) in perikarya of these CA2/3 neurons (r = -0.85, P < 0.01) suggests that nNOS expression may provide selective resistance to neuronal degeneration in AD. In conclusion, our results imply that an upregulated production of NO by reactive astrocytes may play a key role in the pathogenesis of AD.

Extracted Key Phrases

6 Figures and Tables

Showing 1-10 of 72 references

Absence of apoptosis but increased DNA fragmentation in subregions of the Alzheimer hippocampus: Relationship to patterns of cell loss and nNOS immunoreactivity

  • P J Lucassen, G S Imicimic, E R De Kloet, B Winblad, N Bogdanovicbogdanovic
  • 1998
Showing 1-10 of 19 extracted citations

Statistics

0204060'05'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

91 Citations

Semantic Scholar estimates that this publication has received between 28 and 232 citations based on the available data.

See our FAQ for additional information.