A detailed analysis of the early context extinction deficits seen in APPswe/PS1dE9 female mice and their relevance to preclinical Alzheimer's disease

Bonardi, Charlotte; Pulford, Felicity de; Jennings, Dómhnall J.; Pardon, Marie‐Christine

doi:10.1016/j.bbr.2011.03.041

Cited by 57 publications

(66 citation statements)

References 54 publications

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“…In contrast, in Experiment 1 mice of the same age were not significantly impaired on a relative recency task, supposedly a measure of self-generated priming [52]. In both experiments the transgenic mice performed normally on the SOR task, mirroring previous work using animals of this age [40,42]. These results, although preliminary, are consistent with the suggestion that the mice suffer a selective deficit in retrieval-but not self-generated priming at 5 months of age, and that it is only at 6 months of age that the selfgenerated priming condition is also affected, and hence a net impairment in SOR observed.…”

Section: Discussionsupporting

confidence: 60%

“…This widely-used task has revealed deficits in a wide range of different 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 transgenic models of AD [32], and impairments are routinely observed in older APPswe/PS1dE9 mice [33,34,35,36,37; but see 38]. SOR deficits are also occasionally reported in these mice at 6-7 months of age [34,39,40,41], but never in animals younger than 6 months [40,42]. As elevated levels of Aβ are present from around 3.5 months of age in this strain [6,7], it is difficult to explain the SOR deficits in terms of this factor.…”

Section: Introductionmentioning

confidence: 99%

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Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: Implications for object recognition

Bonardi

Pardon

Armstrong

2016

Behavioural Brain Research

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Performance was examined on three variants of the spontaneous object recognition (SOR) task, in 5-month old APPswe/PS1dE9 mice and wild-type littermate controls. A deficit was observed in an object-in-place (OIP) task, in which mice are preexposed to four different objects in specific locations, and then at test two of the objects swap locations (Experiment 2). Typically more exploration is seen of the objects which have switched location, which is taken as evidence of a retrieval-generated priming mechanism. However, no significant transgenic deficit was found in a relative recency (RR) task (Experiment 1), in which mice are exposed to two different objects in two separate sample phases, and then tested with both objects. Typically more exploration of the firstpresented object is observed, which is taken as evidence of a self-generated priming mechanism. Nor was there any impairment in the simplest variant, the spontaneous object recognition (SOR) task, in which mice are preexposed to one object and then tested with the familiar and a novel object. This was true regardless of whether the sample-test interval was 5 minutes (Experiment 1) or 24 hours (Experiments 1 and 2). It is argued that SOR performance depends on retrieval-generated priming as well as self-generated priming, and our preliminary evidence suggests that the retrieval-generated priming process is especially impaired in these young transgenic animals . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 The aim of our research has been to identify early cognitive signs of AD in one specific genetic model, the double-transgenic APPswe/PS1dE9 mouse. This may be the best-characterised transgenic model of AD to date, co-expressing the mutated Swedish APP gene and also the exon-9 deleted variant of the PS1 gene [5]. Elevated levels of oligomeric Aβ in the cortex and hippocampus have been observed at 3.5 months of age in these mice; these changes are accompanied by synaptic deficits [6,7], and are also closely associated with swollen dystrophic cholinergic neurites [8].Although the amyloid plaques characteristic of AD have been reported at 4 months of age in these mice, it is only from 6 months that they are consistently observed [9]. Aβ deposition is paralleled by progressive degeneration of monaminergic [10,11] and striatal [12] neurons, and neuroinflammatory reactions [13] which mirror human AD pathology. These animals also recapitulate the age-related cognitive decline characteristic of AD [14], which is thought to depend on these neuropathological changes.The neuropathology that develops in AD in general, and in this mouse model in particular, is well specified. But precisely which aspects of this brain pathology underlie the cognitive deficits that are such a central feature of AD is still under debate [15]. In this particular mouse line, some...

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: Implications for object recognition

Bonardi

Pardon

Armstrong

2016

Behavioural Brain Research

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“…Typically these mice display Aβ deposition by 4 months with the appearance of plaques from 6 up to 12 months accompanied by concomitant increase of Aβ levels. Behavioural deficits such as memory deficits typically manifest at 5-6 months of age (35,62,63). This suggests that the effects we may not be consequent to amyloid plaques.…”

Section: Discussionmentioning

confidence: 98%

“…A chimeric mouse/human APP695 with mutations linked to familial AD (APPSwe) was expressed as well as a mutation in the human PS1 gene carrying the exon-9-deleted variant associated with AD (33,34). All experimental animals used in the present work were bred in the University of Nottingham's transgenic animal facility and have been described previously (35,36). Prior to activity monitoring studies, all mice were housed in the same room, maintained on a light/dark (LD) light cycle, with lights on at 07:00 hrs.…”

Section: Animals and Housing Conditionsmentioning

confidence: 99%

Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

Oyegbami

Collins

Pardon

et al. 2017

CAR

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“…All mice were were bred in the University of Nottingham's Biomedical Service Unit as previously described [45]. Some of these mice had been treated 10 days before with a lipopolysaccharide immune challenge (LPS, 100ug/kg) known to selectively activate microglia or its vehicle Phosphate Buffered Saline (PBS, Sigma Aldrich, St. Louis, MO, USA).…”

Section: A Data Acquisitionmentioning

confidence: 99%

Novel Methods for Microglia Segmentation, Feature Extraction, and Classification

Ding

Pardon

Agostini

et al. 2017

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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Abstract-Segmentation and analysis of histological images provides a valuable tool to gain insight into the biology and function of microglial cells in health and disease. Common image segmentation methods are not suitable for inhomogeneous histology image analysis and accurate classification of microglial activation states has remained a challenge. In this paper, we introduce an automated image analysis framework capable of efficiently segmenting microglial cells from histology images and analysing their morphology. The framework makes use of variational methods and the fast-split Bregman algorithm for image denoising and segmentation, and of multifractal analysis for feature extraction to classify microglia by their activation states. Experiments show that the proposed framework is accurate and scalable to large datasets and provides a useful tool for the study of microglial biology.Index Terms-microglia analysis, Mumford-Shah, fast split Bregman, fast Fourier transform, multifractal analysis, histology data analysis.

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A detailed analysis of the early context extinction deficits seen in APPswe/PS1dE9 female mice and their relevance to preclinical Alzheimer's disease

Cited by 57 publications

References 54 publications

Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: Implications for object recognition

Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: Implications for object recognition

Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

Novel Methods for Microglia Segmentation, Feature Extraction, and Classification

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