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Synchrotron infrared microspectroscopy of biological tissues: brain tissue from TgCRND8 Alzheimer’s disease mice and developing scar tissue in rats

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dc.contributor.supervisor Gough, Kathleen (Chemistry) en
dc.contributor.author Rak, Margaret
dc.date.accessioned 2007-04-10T15:33:26Z
dc.date.available 2007-04-10T15:33:26Z
dc.date.issued 2007-04-10T15:33:26Z
dc.identifier.uri http://hdl.handle.net/1993/323
dc.description.abstract Biological tissues were studied with synchrotron infrared (IR) microspectroscopy, a technique that allows the spatially resolved determination and mapping of multiple components in situ at high spatial resolution. The first project involved studying brain tissue from TgCRND8 mice, a transgenic model of Alzheimer’s disease (AD). AD is the main cause of dementia in the ageing population, marked by the deposition of plaques composed of the Aβ peptide. Dense-cored and diffuse plaques were IR mapped and the results correlated with histochemistry and immunostaining. Spectral analysis confirmed that congophilic plaque cores were composed of highly aggregated protein in a β-sheet conformation. The amide I maximum of plaque cores was 1623 cm-1; there was no evidence of the high frequency (1680-1690 cm-1) peak seen in in vitro Aβ fibrils and attributed to anti-parallel β-sheet. A significant elevation in phospholipids was found around dense-cored plaques in TgCRND8 mice ranging in age from 5 to 21 months. This was due to an increase in cellular membranes from dystrophic neurites and glial cells around the core, but could also contribute to Aβ aggregation through the interaction of newly secreted Aβ with phospholipids. In contrast, diffuse plaques were not associated with infrared detectable changes in protein secondary structure or relative concentrations of other tissue components. In addition, focally elevated deposits of creatine, a molecule with a crucial role in energy metabolism, were discovered in AD brain tissue with IR microspectroscopy. The creatine deposits may be a previously undiscovered disease marker. A second project was part of a larger Natural Sciences and Engineering Research Council Collaborative Health Research Project (NSERC-CHRP) to test the hypothesis that treatment with anti-oxidants, L-2-oxo-thiazolidine-4-carboxylate (OTC) and quercetin, following spinal surgery may reduce oxidative stress, inflammation, and scarring. The effect of OTC and quercetin on scar tissue formation was evaluated in rats that had undergone laminectomy. Synchrotron IR microspectroscopy data were collected on scar tissue from OTC, quercetin and saline (control) treated animals, sacrificed at 3 and 21 days post-surgery. Spectral differences could be correlated with the stages of wound healing. en
dc.format.extent 11895765 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject infrared en
dc.subject microspectroscopy en
dc.subject synchrotron en
dc.subject Alzheimer's disease en
dc.subject scar tissue en
dc.subject amyloid en
dc.subject plaques en
dc.subject infrared mapping en
dc.subject TgCRND8 mice en
dc.subject creatine en
dc.title Synchrotron infrared microspectroscopy of biological tissues: brain tissue from TgCRND8 Alzheimer’s disease mice and developing scar tissue in rats en
dc.degree.discipline Chemistry en
dc.contributor.examiningcommittee Albensi, Benedict (Department of Pharmacology and Therapeutics) Holman,Hoi-Ying (Earth Sciences Division, Lawrence Berkeley National Laboratory) Mai, Sabine (Cell Biology/Physiology) Schweizer, Frank (Chemistry) Stetefeld, Jörg (Chemistry) en
dc.degree.level Doctor of Philosophy (Ph.D.) en
dc.description.note May 2007 en


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