Assessing Sex-Specific Circadian, Metabolic, and Cognitive Phenotypes in the AβPP/PS1 and APPNL - F/NL - F Models of Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jesse Britz ◽  
Emmanuel Ojo ◽  
Asmita Dhukhwa ◽  
Takashi Saito ◽  
Takaomi C. Saido ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Cognitive Deficits ◽  
Activity Patterns ◽  
Spatial Learning And Memory ◽  
Plaque Pathology ◽  
Glucose Sensitivity ◽  
Old Females ◽  
Daily Activity Patterns

Background: Circadian disruption has long been recognized as a symptom of Alzheimer’s disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits. Objective: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL - F/NL - F) AD mouse models from the period of plaque initiation (6 months) through 12 months. Methods: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across sexes. Results: Sex-dependent hyperactivity in AβPP/PS1 mice was observed. In comparison to C57BL/6J animals, 6-month-old male AβPP/PS1 demonstrated nighttime hyperactivity, as did 12-month-old females. Female AβPP/PS1 animals performed significantly worse on a MWM task than AβPP/PS1 males at 12 months and trended toward increased plaque pathology. APPNL - F/NL - F 12-month-old males performed significantly worse on the MWM task compared to 12-month-old females. Significantly greater plaque pathology occurred in AβPP/PS1 animals as compared to APPNL - F/NL - F animals. Female AβPP/PS1 animals performed significantly worse than APPNL - F/NL - F animals in spatial learning and memory tasks, though this was reversed in males. Conclusion: Taken together, this study provides novel insights into baseline sex differences, as well as characterizes baseline diurnal activity variations, in the AβPP/PS1 and APPNL - F/NL - F AD mouse models.

scholarly journals Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Yan-Fang Xian ◽  
Chang Qu ◽  
Yue Liu ◽  
Siu-Po Ip ◽  
Qiu-Ju Yuan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Molecular Mechanisms ◽  
Interleukin 10 ◽  
Spatial Learning And Memory ◽  
Necrosis Factor Alpha ◽  
App Processing ◽  
Model Of Alzheimer’S Disease ◽  
Tgcrnd8 Mice

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive memory loss. Magnolol (MN), the main active ingredient of Magnolia officinalis, possesses anti-AD effects in several experimental models of AD. In this study, we aimed to explore whether MN could ameliorate the cognitive deficits in TgCRND8 transgenic mice and to elucidate its molecular mechanisms. Male TgCRND8 mice were orally administered with MN (20 and 40 mg/kg) daily for 4 consecutive months, followed by assessing the spatial learning and memory functions using the open-field, radial arm maze, and novel object recognition tests. The results demonstrated that MN (20 and 40 mg/kg) could markedly ameliorate the cognitive deficits in TgCRND8 mice. In addition, MN significantly increased the expression of postsynaptic density protein 93 (PSD93), PSD-95, synapsin-1, synaptotagmin-1, synaptophysin (SYN), and interleukin-10 (IL-10), while markedly reduced the protein levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-1β, Aβ40, and Aβ42, and modulated the amyloid precursor protein (APP) processing and phosphorylation. Immunofluorescence showed that MN significantly suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the hippocampus and cerebral cortex of TgCRND8 mice. Mechanistic studies revealed that MN could significantly increase the ratios of p-GSK-3β (Ser9)/GSK-3β, p-Akt (Ser473)/Akt, and p-NF-κB p65/NF-κB p65. These findings indicate that MN exerted cognitive deficits improving effects via suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction through regulating the PI3K/Akt/GSK-3β and NF-κB pathways, suggesting that MN is a promising naturally occurring polyphenol worthy of further developing into a therapeutic agent for AD treatment.

P1-022: Cellular mechanisms underlying aberrant EEG activity and cognitive deficits in mouse models of Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_6) ◽  
pp. P178-P178
Author(s):  
Peter Reinhart ◽  
Steven Leiser ◽  
Huai-Ping Ling ◽  
Jon Brown ◽  
Tom Comery ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Cognitive Deficits ◽  
Cellular Mechanisms ◽  
Eeg Activity

scholarly journals Brain Cellular Senescence in Mouse Models of Alzheimer's Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 937-937
Author(s):  
Ruben Riordan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Cellular Senescence ◽  
Cognitive Deficits ◽  
Matched Control ◽  
Wild Type ◽  
Expected Time ◽  
Do So

Abstract The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild type mice as well as in Alzheimer’s disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models, and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models is not yet known. The goal of this study was to identify mouse models of AD and AD-related dementias that develop measurable markers of cellular senescence in brain and thus may be useful to study the role of cellular senescence in these conditions. We measured levels of cellular senescence markers in brains of P301S(PS19), P301L, hTau, and 3xTg-AD mice that model amyloidopathy and/or tauopathy in AD and related dementias, and in wild type, age-matched control mice for each strain. Expression of cellular senescence markers in brains of transgenic P301L and 3xTg-AD mice was largely indistinguishable from that in WT control age-matched mice. In contrast, markers of cellular senescence were significantly increased in brains of transgenic P301S and hTau mice as compared to WT control mice at the expected time of onset of AD-like cognitive deficits. Taken together, our data suggest that P301S(PS19) and hTau mice may be useful for the study of brain cellular senescence in tauopathies including, but not limited to, AD.

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