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 rhesus monkey is a model of normal human aging that enables cognitive testing to be followed by optimal preservation of brain tissue for multidisciplinary studies. These ongoing studies test the hypothesis that age-related cognitive decline results from a cascade of mild degenerative changes beginning in early middle age with inflammation and damage in white matter that leads to functional changes in axons and progresses to functional and structural changes in neurons. Three cohorts of monkeys are being studied to test various aspects of this hypothesis. After behavioral testing of the first cohort, MRI scans are followed by in vivo neurophysiology and perfusion fixation to provide fresh and fixed tissue to identify brain changes underlying cognitive decline. A second cohort of 6 middle aged monkeys is being treated like cohort 1 except their samples will be perfusion fixed with mixed aldehydes for electron microscopy to supplement existing samples and allow identification of the ultrastructural changes. A third cohort of 12 early middle aged monkeys (ages 13-15) is being followed longitudinally for with repeated behavioral testing, MRI scans of the brain, and analysis of blood and CSF. Longitudinal MRIs will reveal concurrent changes in the in vivo brain structure, and CSF and blood samples will allow biomarkers to be followed. For cohorts 1 and 3, perfusion fixation is preceded by in vivo neurophysiological assessment of compound action potentials. Two stage perfusion follows to allow immediate collection of unfixed samples from one hemisphere before the remainder of the brain is fixed. Fixed tissue is used for anatomical studies, including stereological studies of neuron numbers and immunocytochemical studies of inflammation and other degenerative processes. Structures of key proteins are being determined by FTMS and LC-MS/MS.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-H (40))
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Boston University
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Wang, Yun Hwa Walter; Meyer, Rosana D; Bondzie, Philip A et al. (2016) IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function. J Mol Biol 428:5019-5033
Pu, Yi; Ridgeway, Mark E; Glaskin, Rebecca S et al. (2016) Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry. Anal Chem 88:3440-3
Hu, Han; Khatri, Kshitij; Klein, Joshua et al. (2016) A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J 33:285-96
Ji, Yuhuan; Bachschmid, Markus M; Costello, Catherine E et al. (2016) S- to N-Palmitoyl Transfer During Proteomic Sample Preparation. J Am Soc Mass Spectrom 27:677-85
Rahimi, Nader; Costello, Catherine E (2015) Emerging roles of post-translational modifications in signal transduction and angiogenesis. Proteomics 15:300-9
Théberge, Roger; Dikler, Sergei; Heckendorf, Christian et al. (2015) MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies. J Am Soc Mass Spectrom 26:1299-310
Yu, Xiang; Sargaeva, Nadezda P; Thompson, Christopher J et al. (2015) In-Source Decay Characterization of Isoaspartate and β-Peptides. Int J Mass Spectrom 390:101-109
Walsh, Erica M; Niu, MengMeng; Bergholz, Johann et al. (2015) Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation. Biochem Biophys Res Commun 461:293-9
Steinhorn, Benjamin S; Loscalzo, Joseph; Michel, Thomas (2015) Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med 373:277-80
Srinivasan, Srimathi; Chitalia, Vipul; Meyer, Rosana D et al. (2015) Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis 18:449-62

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