This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term goal of the proposed research is to develop a rational basis for neuroprotective strategies to delay or to prevent the onset of Alzheimer's disease (AD). Studies of mitochondrial function have shown mitochondrial abnormalities in postmortem brains in AD patients and imaging studies of brains from presymptomatic AD patients, suggesting that defects in cerebral energy metabolism may be a key factor in the development and progression of AD. Recent global gene expression studies have revealed an up-regulation of mitochondrial genes in 2-, 5- and 18-month-old mice from AD transgenic mouse line Tg2576, suggesting that mitochondria energy metabolism may be impaired by mutant amyloid precursor protein/Abeta (APP/A?) and that the up-regulation of mitochondrial gene expression may be a compensatory response to mutant APP/A? toxicity. In addition, biochemical studies have revealed increases in H2O2 production, oxidized DNA and proteins in Tg2576 mice compared to wild-type (wt) mice, also providing support that oxidative damage occurs in the AD mice. The proposed studies are pursuing the hypothesis that A? is a major factor in generating ROS and mitochondrial dysfunction. The following Specific Aims are investigating this hypothesis:
Aim 1. To determine whether mitochondrial dysfunction triggers mitochondrial gene expression in Tg2576 mice;
Aim 2. To determine whether mutant APP and/or A? leads to oxidative damage in Tg2576 mice;
and Aim 3. To determine whether mitochondrially targeted antioxidant catalase reduces ROS, mitochondrial toxicity and A? levels in Tg2576 mice and in an APP over-expressed cell-line model.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357796
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$58,239
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Su, Weiping; Foster, Scott C; Xing, Rubing et al. (2017) CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation. J Biol Chem 292:4434-4445
Lima, Fernanda B; Leite, Cristiane M; Bethea, Cynthia L et al. (2017) Progesterone increased ?-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration. Brain Res 1663:1-8
Slayden, Ov Daniel (2016) Translational In Vivo Models for Women's Health: The Nonhuman Primate Endometrium--A Predictive Model for Assessing Steroid Receptor Modulators. Handb Exp Pharmacol 232:191-202
Chadderdon, S M; Belcik, J T; Bader, L et al. (2016) Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes (Lond) 40:1600-1603
Dufour, Brett D; McBride, Jodi L (2016) Intravascular AAV9 Administration for Delivering RNA Silencing Constructs to the CNS and Periphery. Methods Mol Biol 1364:261-75
Meyer, Thomas J; Held, Ulrike; Nevonen, Kimberly A et al. (2016) The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery. Genome Biol Evol 8:3209-3225
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C et al. (2016) Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun 7:11138
Sylwester, Andrew; Nambiar, Kate Z; Caserta, Stefano et al. (2016) A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev 158:14-22
Laws, L H; Parker, C E; Cherala, G et al. (2016) Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion. Am J Transplant 16:3139-3149

Showing the most recent 10 out of 481 publications