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Validation of the IntelliCage as a new bahavioural paradigm for miceWoodcock, Hilary January 2011 (has links)
The aims of this thesis were to investigate and validate the IntelliCage (New Behaviour, Zurich, Switzerland) as a new behavioural testing system using two different protocols. 1- Determining differences in activity and spatial learning in genetically altered PLB1 mice that express different features of Alzheimer’s disease and genes, assess their ability to learn the location of a designated water source (corner) within the IntelliCage. Different genotypes were used i.e PLB1wt (control),PLB1tau,PLB1Double (APP & TAU),PLB1Triple (APP, TAU & PSEN) and PLB1APP, and 3 different age groups (5,12 and 20 months). 2- Assessment of drug-induced changes in activity and spatial learning in two strains of mice (C57BL/6 and DBA) at approximately 6 weeks of age. Four different drug treatments, injected intraperitoneally prior to the beginning of the dark cycle were studied i.e, Apomorphine 6.4mg/kg (APO), Phencyclidine 1mg/kg & 4mg/kg (PCP), Scopolamine 0.5mg/kg (scop) and saline (vehicle). Parameters investigated included overall visits (habituation and training) and correct visits to trained corner. Our results indicate that the IntelliCage is sensitive enough to detect strain differences in reference to activity levels, spatial learning and drug treatments. It was particularly obvious in the PLB1 study that the IntelliCage can detect deficits in different age groups as it was possible to see learning differences within genotypes over three age groups. The IntelliCage can detect learning deficits in the 5 and 12 months groups, and confirms that all genotypes including the controls do not show learning at 20 months. With reference to the drug experiments, determination of drug wash out periods was assessed by manipulating the data into hourly bins. Treating groups with different drugs also produced different effects between strains; the C57BL/6 mice were most affected by APO during assessment of overall activity whereas the DBA mice’s behaviour was most affected by both PCP treatments. Investigation of spatial learning has revealed the C57BL/6 groups all performed reliably above chance (25%) and showed a significant increase in trained corner visits post drug, the DBA groups all failed to reliably learn above chance (25%) during 12 hours post drug injection. Comparing strains found that the only drug to cause an interaction was APO. It is possible to confirm that the IntelliCage is only useful for detecting genotype differences and drug effects on the C57BL/6 strain as no significant differences can be seen between the DBA drug treated groups.
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Therapeutic and functional studies in animal models of Alzheimer's diseaseGumucio, Astrid January 2014 (has links)
Senile plaques (Aβ) and neurofibrillary tangles (tau) are pathological hallmarks of Alzheimer’s disease (AD). If and how the formation of these deposits are mechanistically linked remains mainly unknown. In recent years, the focus has shifted from insoluble protein deposits to soluble aggregates of Aβ and tau. Protofibrils are large soluble Aβ oligomers which were linked to AD by the discovery of the Arctic AβPP mutation. Treatment of young tg-ArcSwe mice with an Aβ protofibril-selective antibody, mAb158, cleared protofibrils, prevented amyloid plaque deposition and protected cultured cells from protofibril-mediated toxicity. This suggests that Aβ protofibrils are necessary for the formation of Aβ deposits. Functional assessment of tg-ArcSwe mice in IntelliCage demonstrated hippocampal-dependent behavioral deficits such as memory/learning impairments, hyperactivity and perseverance behavior. Learning impairments did not correlate to Aβ-measures but to calbindin, which might be a good marker for Aβ-mediated neuronal dysfunction. Splicing of exon 10 in the tau gene differs between human and mouse brain. Exon 10 is part of the microtubule-binding domains which helps to maintain microtubule stability and axonal transport, functions vital to neuronal viability. Axonal transport dysfunction has been proposed as a common pathway of Aβ and tau pathogenesis in AD. Generation of a novel tau mouse model with absence of exon 10 led to age-dependent sensorimotor impairments which may relate to dysfunctions in cerebellum. No tau pathology was evident suggesting that a trigger of tau fibrillization e.g. a human Aβ or tau aggregate is needed. Generation of AβPPxE10 bitransgenic mice with no exon 10 showed lower Aβ plaque burden. Possibly changes in microtubule function lead to altered intracellular AβPP transport and Aβ production. Initiation of tau pathology in AβPPxE10 mice might require a certain type of Aβ-aggregates which is not produced or exist at too low concentration in transgenic mouse brain. In summary, the Aβ protofibril-selective antibody was found to be a promising treatment for AD. The IntelliCage system was proven to be useful for functional evaluation of AβPP mice. Exon 10 in tau was shown to affect sensorimotor functions and Aβ pathology in bitransgenic mice by mechanisms that deserve further investigation.
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Porovnání transgenního a streptozotocinového modelu Alzheimerovy choroby: validace systému IntelliCage pro behaviorální fenotypizaci / Comparison of transgenic and streptozotocin models of Alzheimer in rats: validation of IntelliCage system for behavioral phenotypizationSvobodová, Eva January 2021 (has links)
Animal models of Alzheimer's disease display cognitive insufficiencies which mimic human symptoms and occur at a given age or post-treatment time. Animals are typically tested using canonical behavioral tests, lasting minutes and taking place mostly in the non-active period of the daily cycle. Animals are exposed to certain amounts of manipulation-induced stress. Our work represents a validation study for the rat behavioral system IntelliCage. The tested individuals live freely in a group and their behavior is monitored continuously. It is however possible to set up individual tests for each animal or a group of animals. The rats are not subject to human manipulation and hence the results are not affected by manipulation-induced stress. We tested early cognitive impairment in the transgenic rat model TgF344-AD at 6 - 8 months of age. Further, we tested two most common protocols of the streptozotocin model, i.e. single dose of intracerebroventricular 3 mg/kg streptozotocin and double dose 48 hrs apart. Results were compared with the canonical Morris Water Maze (MWM) test. In the MWM test, transgenic animals did not differ from controls in any of the studied parameters. The streptozotocin model displayed a deficit only in the double dose group. However in the IntelliCage, transgenic animals displayed...
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