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Alzheimer's disease: an evaluation of memory and neuropathology in the TgCRND8 transgenic mouse modelGlazner, Kathryn A.C. 19 June 2010 (has links)
Alzheimer’s disease (AD) is a neurologically debilitating disease that is plaguing our elderly population. Transgenic mice with Alzheimer’s disease mutations are used to study signal pathways, potential drug targets and mechanism of disease. However, studies of the effects of different AD mutations on behavior and neuropathological progression in mice have been inconsistent when comparing different genetic backgrounds. The aim of this study was to compare two commonly used TgCRND8 backgrounds, the 129SvEvtac/C57F1 and C3H/C57F1 strains, for memory function in the Morris water maze (MWM), and to determine differences in plaque burden. We found deficits in multiple parameters of the MWM in the 129SvEvtac/C57F1 strain. Similarly, this background strain showed significantly more amyloid beta (Aβ) plaque burden than the C3H/C57F1 strain. This supports the hypothesis that strain specific differences are apparent in spatial memory testing and neuropathologic progression of AD. It leads us to believe that epigenetics are key to understanding AD risk assessment and development.
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Alzheimer's disease: an evaluation of memory and neuropathology in the TgCRND8 transgenic mouse modelGlazner, Kathryn A.C. 19 June 2010 (has links)
Alzheimer’s disease (AD) is a neurologically debilitating disease that is plaguing our elderly population. Transgenic mice with Alzheimer’s disease mutations are used to study signal pathways, potential drug targets and mechanism of disease. However, studies of the effects of different AD mutations on behavior and neuropathological progression in mice have been inconsistent when comparing different genetic backgrounds. The aim of this study was to compare two commonly used TgCRND8 backgrounds, the 129SvEvtac/C57F1 and C3H/C57F1 strains, for memory function in the Morris water maze (MWM), and to determine differences in plaque burden. We found deficits in multiple parameters of the MWM in the 129SvEvtac/C57F1 strain. Similarly, this background strain showed significantly more amyloid beta (Aβ) plaque burden than the C3H/C57F1 strain. This supports the hypothesis that strain specific differences are apparent in spatial memory testing and neuropathologic progression of AD. It leads us to believe that epigenetics are key to understanding AD risk assessment and development.
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Examination of Creatine deposits and Environs in TgCRND8 Mouse Brain by Raman and FTIR MicrospectroscopyKhamenehfar, Avid 27 July 2011 (has links)
Alzheimer Disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and dementia. Both energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain. With synchrotron FTIR microscopy, extensive deposits of crystalline creatine (Cr) had been discovered in TgCRND8 mouse brain tissue by previous students in our lab.
In this thesis, regions of hippocampus and caudate of 5 pairs of transgenic mice and their non-transgenic littermate controls were mapped using Raman and IR microspectroscopy to find clues to Cr origin in transgenic mouse brain. Raman spectra obtained at higher spatial resolution (1-2 µm) were used for better delineation of the Cr crystalline deposits and their environs.
These results indicate that Cr crystals were formed after snap-freezing and desiccation of brain tissue. Therefore, it can be speculated that Cr might be exist in solution form in vivo.
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Examination of Creatine deposits and Environs in TgCRND8 Mouse Brain by Raman and FTIR MicrospectroscopyKhamenehfar, Avid 27 July 2011 (has links)
Alzheimer Disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and dementia. Both energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain. With synchrotron FTIR microscopy, extensive deposits of crystalline creatine (Cr) had been discovered in TgCRND8 mouse brain tissue by previous students in our lab.
In this thesis, regions of hippocampus and caudate of 5 pairs of transgenic mice and their non-transgenic littermate controls were mapped using Raman and IR microspectroscopy to find clues to Cr origin in transgenic mouse brain. Raman spectra obtained at higher spatial resolution (1-2 µm) were used for better delineation of the Cr crystalline deposits and their environs.
These results indicate that Cr crystals were formed after snap-freezing and desiccation of brain tissue. Therefore, it can be speculated that Cr might be exist in solution form in vivo.
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Synchrotron infrared microspectroscopy of biological tissues: brain tissue from TgCRND8 Alzheimer’s disease mice and developing scar tissue in ratsRak, Margaret 10 April 2007 (has links)
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. / May 2007
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Synchrotron infrared microspectroscopy of biological tissues: brain tissue from TgCRND8 Alzheimer’s disease mice and developing scar tissue in ratsRak, Margaret 10 April 2007 (has links)
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.
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Synchrotron infrared microspectroscopy of biological tissues: brain tissue from TgCRND8 Alzheimer’s disease mice and developing scar tissue in ratsRak, Margaret 10 April 2007 (has links)
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.
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Use of Dietary Supplementation of Unsaturated Fatty Acids to Delay Onset of Learning and Memory Deficits in TgCRND8 MiceFranko, Bettina January 2014 (has links)
Alzheimer’s disease (AD) is a complex neurodegenerative disorder, involving metabolic dysfunction, pathogenic aggregation of amyloid beta, and deteriorating cognitive function. Patients exhibit deficiency in omega-3,-6,-9 unsaturated fatty acids (UFAs) in plasma and brain membrane phospholipids, suggesting aberrant fatty acid metabolism influences pathology. Cognitive benefits of omega UFAs in AD remain unknown. Here, I examined effects of a four-month dietary supplementation with UFAs for capacity to alter learning and memory behaviour in an AD mouse model. Cognitive impairment in a fifth generation backcross (N5) C57BL/6Crl X C3H/HeJ TgCRND8 (Tg) mice was compared to control (NonTg) littermates, with respect to both males and females, at six months of age using the Morris Water Maze (MWM). Impairment differed between sexes; female Tg mice were severely impaired, whereas male Tg mice displayed delayed learning. A reduced visual acuity in Tg and NonTg mice, shown by adapted SLAG reflex test, did not impair spatial navigation in cued MWM. A four-month omega-6/-9 UFA oral treatment (75 mg/kg/day) improved learning and memory of Tg mice as compared to vehicle and untreated controls. Omega-3 UFAs, or vehicle alone, did not alter learning and memory of Tg and NonTg mice. Thus, dietary supplementation, particularly when enriched in omega-6/9 UFAs, can affect neural function, and delay conversion from a presymptomatic to symptomatic state in the TgCRND8 mouse model.
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Implication des métabolites de l'APP dans les troubles mnésiques précoces chez la souris TgCRND8, un modèle de la maladie d'Alzheimer / Differential contribution of APP metabolites to early memory deficits in a TgCRND8 mouse model of Alzheimer’s diseaseHamm - Haouari, Valentine 06 December 2016 (has links)
La maladie d’Alzheimer (MA) est une pathologie neurodégénérative communément caractérisée par une perte progressive de la mémoire. L’étiologie de la MA demeure incertaine à ce jour ce qui complique l’élaboration de stratégies thérapeutiques permettant de l’éradiquer. L’accumulation des échecs thérapeutiques pourrait en partie s’expliquer par le fait que l’hypothèse amyloïde, qui met en avant l’implication prépondérante du peptide bêta-amyloïde (Aβ) dans la physiopathologie de la MA, serait incomplète. En utilisant un modèle murin transgénique de la MA, la souris TgCRND8, j’ai pu compléter l’hypothèse amyloïde en proposant l’implication, en plus de l’Aβ, du fragment carboxy-terminal bêta (β-CTF). Ces deux métabolites amyloïdogéniques de l’APP seraient responsables de l’altération de formes différentes de mémoire. Le dosage de ces métabolites dans l’hippocampe, suite au traitement chronique des souris avec un inhibiteur de β ou de γ-secrétase, a mis en évidence que le β-CTF serait responsable de l’atteinte de la mémoire impliquée dans la détection du remplacement d’un objet, alors que l’Aβ perturberait la mémoire permettant la détection du déplacement d’un objet. Ces travaux suggèrent qu’il serait judicieux de développer de nouvelles stratégies thérapeutiques qui diminuent à la fois les niveaux cérébraux des deux fragments amyloïdogéniques, le β-CTF et l’Aβ. / Alzheimer’s disease (AD) is a neurodegenerative pathology commonly characterized by a progressive memory loss. To these days, AD’s etiology has remained unclear which complicates the development of therapeutic strategies enabling to eradicate the pathology. The accumulation of therapeutic failures could partly be explained by the fact that the amyloid hypothesis, which highlights the leading involvement of the amyloid beta peptide (Aβ) in the physiopathology of AD, could be incomplete. Using a transgenic mouse model of AD, the TgCRND8 mice strain, I expanded the amyloid hypothesis, suggesting the involvement of the beta carboxy-terminal fragment (β-CTF), in addition to Aβ. These two amyloidogenic metabolites could be responsible for the alteration of different forms of memory. The dosage of these metabolites, after mice chronic treatment with either a β- or a γ-secretase inhibitor, highlighted the fact that β-CTF could be responsible for the deterioration of the memory involved in the detection of the replacement of an object. As for Aβ, it could disrupt the memory allowing the detection of the displacement of an object. This work suggests that it would be judicious to develop therapeutic strategies reducing brain levels of both amyloid fragments, β-CTF and Aβ.
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