한빛사논문
- 조회1,886
Abstract
, Carmen Capone*, Josef Anrather*, Erin H. Norris
, Linda Younkin
, Steven Younkin, George Carlson, Bruce S. McEwen,¶, and Costantino Iadecola*,¶
*Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065; Mayo Clinic Jacksonville, Jacksonville, FL 32224; and McLaughlin Research Institute, Great Falls, MT 59405
Contributed by Bruce S. McEwen, December 7, 2007 (sent for review October 23, 2007)
Abstract
Alterations in cerebrovascular regulation related to vascular oxidative stress have been implicated in the mechanisms of Alzheimer''s disease (AD), but their role in the amyloid deposition and cognitive impairment associated with AD remains unclear. We used mice overexpressing the Swedish mutation of the amyloid precursor protein (Tg2576) as a model of AD to examine the role of reactive oxygen species produced by NADPH oxidase in the cerebrovascular alterations, amyloid deposition, and behavioral deficits observed in these mice. We found that 12- to 15-month-old Tg2576 mice lacking the catalytic subunit Nox2 of NADPH oxidase do not develop oxidative stress, cerebrovascular dysfunction, or behavioral deficits. These improvements occurred without reductions in brain amyloid-β peptide (Aβ) levels or amyloid plaques. The findings unveil a previously unrecognized role of Nox2-derived radicals in the behavioral deficits of Tg2576 mice and provide a link between the neurovascular dysfunction and cognitive decline associated with amyloid pathology.
Alzheimer''s disease | cerebral blood flow | tg2576
Footnotes
Author contributions: L.P., P.Z., J.A., G.C., B.S.M., and C.I. designed research; L.P., R.P., C.C., L.Y., and S.Y. performed research; P.Z., J.A., E.H.N., L.Y., S.Y., G.C., and B.S.M. contributed new reagents/analytic tools; L.P., S.Y., B.S.M., G.C., and C.I. analyzed data; and L.P., G.C., B.S.M., and C.I. wrote the paper.
The authors declare no conflict of interest.
¶To whom correspondence may be addressed.
논문정보
- Research article
- 2008년 01월 (BRIC 등록일 )
- 국외 연구진
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