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Pregled bibliografske jedinice broj: 39275

Časopis

Autori: Šimić, Goran; Lucassen, Paul; Krsnik, Željka; Krušlin, Božo; Kostović, Ivica; Winblad, Bengt; Bogdanović, Nenad
Naslov: nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's disease
Izvornik: Experimental neurology (0014-4886) 165 (2000), 1; 12-26
Vrsta rada: članak
Ključne riječi: Alzheimer's disease; astrocytes; brain nitric oxide synthase; DNA damage; entorhinal cortex; hippocampus; immunocytochemistry; in situ end-labeling
Sažetak:
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 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 CA2/3 pyramidal neurons was found to be spared even in the most affected hippocampi. A significant inverse correlation between nNOS expression and immunoreactivity to abnormally phophorylated tau proteins (as revealed by AT8 monoclonal antibody) in perikarya of these CA2/3 neurons (r=-0.85, P<0.01) suggest 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.
Projekt / tema: 0108118
Izvorni jezik: ENG
Rad je citiran u
bazama podataka:
Web of Science: Science Citation
Current Contents Citation Index
Scopus
MEDLINE
Web of Science: Science Citation Index Expanded
Kategorija: Znanstveni
Znanstvena područja:
Temeljne medicinske znanosti,Kliničke medicinske znanosti
Puni text rada: 39275.39275.pdf
URL cjelovitog teksta:
Google Scholar: nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's disease



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