Nitric Oxide Activity and Isoenzyme Expression in the Senescence-Accelerated Mouse P8 Model of Alzheimer's Disease: Effects of Anti-Amyloid Antibody and Antisense Treatments
Open Access
- 16 June 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journals of Gerontology: Series A
- Vol. 64A (10), 1025-1030
- https://doi.org/10.1093/gerona/glp074
Abstract
Amyloid beta protein (Aβ) in Alzheimer’s disease induces oxidative stress through several mechanisms, including stimulation of nitric oxide synthase (NOS) activity. We examined NOS activity and expression in the senescence-accelerated mouse P8 (SAMP8) line. The SAMP8 strain develops with aging cognitive impairments, increases in Aβ, and oxidative stress, all reversed by amyloid precursor protein antisense or Aβ antibody treatment. We found here that hippocampal NOS activity in 12-month-old SAMP8 mice was nearly double that of 2-month-old SAMP8 or CD-1 mice, but with no change in NOS isoenzyme mRNA and protein levels. Antisense or antibody treatment further increased NOS activity in aged SAMP8 mice. Antisense treatment increased inducible NOS (iNOS) mRNA levels, decreased neuronal NOS mRNA and protein levels, but did not affect endothelial NOS (eNOS) or iNOS protein or eNOS mRNA levels. These results suggest a complex relation between Aβ and NOS in the SAMP8 that is largely mediated through posttranslational mechanisms.Keywords
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