Effects of gintonin-enriched fraction on hippocampal cell proliferation in wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease

2016 ◽  
Vol 101 ◽  
pp. 56-65 ◽  
Author(s):  
Hyeon-Joong Kim ◽  
Dae-Joong Kim ◽  
Eun-Ju Shin ◽  
Byung-Hwan Lee ◽  
Sun-Hye Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Proliferation ◽  
Mouse Model ◽  
Wild Type ◽  
Hippocampal Cell ◽  
Model Of Alzheimer’S Disease

Effect of Soluble Amyloid Precursor Protein-alpha on Adult Hippocampal Neurogenesis in a Mouse Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
Shane M. Ohline ◽  
Connie Chan ◽  
Lucia Schoderboeck ◽  
Hollie E. Wicky ◽  
Warren P. Tate ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Hippocampal Neurogenesis ◽  
Precursor Protein ◽  
Adult Hippocampal Neurogenesis ◽  
Wild Type ◽  
Viral Expression ◽  
Model Of Alzheimer’S Disease

Abstract Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer’s disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8 month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU+-labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.

scholarly journals Physical Activity Ameliorates Impaired Hippocampal Neurogenesis in the Tg4-42 Mouse Model of Alzheimer’s Disease

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141989269 ◽  
Author(s):  
Anna-Lina Gerberding ◽  
Silvia Zampar ◽  
Martina Stazi ◽  
David Liebetanz ◽  
Oliver Wirths
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
Hippocampal Neurogenesis ◽  
Wild Type ◽  
Running Wheel ◽  
Model Of Alzheimer’S Disease

There is growing evidence from epidemiological studies that especially midlife physical activity might exert a positive influence on the risk and progression of Alzheimer’s disease. In this study, the Tg4-42 mouse model of Alzheimer’s disease has been utilized to assess the effect of different housing conditions on structural changes in the hippocampus. Focusing on the dentate gyrus, we demonstrate that 6-month-old Tg4-42 mice have a reduced number of newborn neurons in comparison to age-matched wild-type mice. Housing these mice for 4 months with either unlimited or intermittent access to a running wheel resulted in a significant rescue of dentate gyrus neurogenesis. Although neither dentate gyrus volume nor neuron number could be modified in this Alzheimer’s disease mouse model, unrestricted access to a running wheel significantly increased dentate gyrus volume and granule cell number in wild-type mice.

scholarly journals Reducing tau ameliorates behavioural and transcriptional deficits in a novel model of Alzheimer’s disease

2018 ◽  
Author(s):  
Eleanor K Pickett ◽  
Abigail G Herrmann ◽  
Jamie McQueen ◽  
Kimberly Abt ◽  
Owen Dando ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Synaptic Function ◽  
List Type ◽  
Wild Type ◽  
Disease Phenotypes ◽  
Model Of Alzheimer’S Disease ◽  
Novel Model ◽  
Behavioural Deficits

SummaryOne of the key knowledge gaps blocking development of effective therapeutics for Alzheimer’s disease (AD) is the lack of understanding of how amyloid beta (Aβ) and tau cooperate in causing disease phenotypes. Within a mouse tau deficient background, we probed the molecular, cellular and behavioural disruption triggered by wild-type human tau’s influence on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity phenotype and to cause downregulation of gene transcription including many involved in synaptic function. In both our mouse model and in human post-mortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau depletion in the mice, initiated after behavioural deficits emerge, was found to correct behavioural deficits, reduce synaptic tau levels, and substantially reverse transcriptional perturbations, suggesting that lowering tau levels, particularly at the synapse, may be beneficial in AD.Highlights- Expression of human familial Alzheimer’s associated mutant amyloid precursor protein and presenillin 1 with wild-type human tau in the absence of endogenous tau in a novel MAPT-AD mouse model results in behavioural deficits and downregulation of genes involved in synaptic function.- Tau is present in pre and postsynaptic terminals in MAPT-AD mice and human AD brain. In mice, lowering synaptic tau levels was associated with improved cognition and recovered gene expression.- These data suggest that Aβ and tau act cooperatively in impairing synaptic function and that lowering tau at synapses could be a beneficial therapeutic approach in AD.

scholarly journals Neural oscillations during cognitive processes in an App knock-in mouse model of Alzheimer’s disease pathology

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sofia Jacob ◽  
Gethin Davies ◽  
Marijke De Bock ◽  
Bart Hermans ◽  
Cindy Wintmolders ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Home Environment ◽  
Amyloid Β ◽  
Wild Type ◽  
Model Of Alzheimer’S Disease ◽  
Age Dependent ◽  
In The Wild ◽  
Phase Amplitude

Abstract Multiple animal models have been created to gain insight into Alzheimer’s disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid β plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations. Therefore, we investigated in the present study the AppNL-G-Fmodel, an App knock-in (App-KI) mouse model that develops amyloidosis in the absence of APP-overexpression. Our findings at the behavioral, electrophysiological, and histopathological level confirmed an age-dependent increase in Aβ1–42 levels and plaque deposition in these mice in accordance with previous reports. This had apparently no consequences on cognitive performance in a visual discrimination (VD) task, which was largely unaffected in AppNL-G-F mice at the ages tested. Additionally, we investigated neurophysiological functioning of several brain areas by phase-amplitude coupling (PAC) analysis, a measure associated with adequate cognitive functioning, during the VD task (starting at 4.5 months) and the exploration of home environment (at 5 and 8 months of age). While we did not detect age-dependent changes in PAC during home environment exploration for both the wild-type and the AppNL-G-F mice, we did observe subtle changes in PAC in the wild-type mice that were not present in the AppNL-G-F mice.

IFN‐γ enhances neurogenesis in wild‐type mice and in a mouse model of Alzheimer's disease

2008 ◽  
Vol 22 (8) ◽  
pp. 2843-2852 ◽  
Author(s):  
Rona Baron ◽  
Anna Nemirovsky ◽  
Idan Harpaz ◽  
Hagit Cohen ◽  
Trevor Owens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Wild Type ◽  
Model Of Alzheimer’S Disease ◽  
Ifn Γ

scholarly journals Age-related changes in social behaviours in the 5xFAD mouse model of Alzheimer’s disease

2018 ◽  
Author(s):  
Filip Kosel ◽  
Paula Torres Munoz ◽  
J. Renee Yang ◽  
Aimee A. Wong ◽  
Tamara B. Franklin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Social Interactions ◽  
Scent Marking ◽  
Wild Type ◽  
Social Investigation ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
5Xfad Mouse

AbstractIn addition to memory impairments, patients with Alzheimer’s disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wildtype controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.

scholarly journals Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer’s disease

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Shane M. Ohline ◽  
Connie Chan ◽  
Lucia Schoderboeck ◽  
Hollie E. Wicky ◽  
Warren P. Tate ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Hippocampal Neurogenesis ◽  
Precursor Protein ◽  
Adult Hippocampal Neurogenesis ◽  
Wild Type ◽  
Viral Expression ◽  
Model Of Alzheimer’S Disease

AbstractSoluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer’s disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8-month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU+-labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.

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