Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

Zou, Yan; Yu, Li; Yu, Weihua; Du, Yingshi; Shi, Rui; Zhang, Man; Duan, Jingxi; Deng, Yongtao; Tu, Qiuyun; Dai, Rong; Lü, Yang

doi:10.1159/000351669

Cited by 3 publications

(2 citation statements)

References 60 publications

(30 reference statements)

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“…In APP/PS1 double transgenic mice, mitochondrial morphology has been shown to be altered in our previous study [12]. It is understandable that mitochondrial morphology damage causes dysfunction.…”

Section: Discussionmentioning

confidence: 71%

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Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

et al. 2015

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Emerging data suggests that mitochondrial dysfunction is prominently involved in Alzheimer disease (AD) progression. Sirtuin-3 (Sirt3) is a member of the sirtuin family of nicotinamide adenine dinucleotide dependent deacetylases that regulates a variety of mitochondrial functions and suppresses mitochondria-related physiology. Here, we determined sirt3 expression in a mouse model of AD. Spatial learning and memory were tested by Morris water maze in APP/PS1 double transgenic mice. The expression of sirt3 was assayed by real-time quantitative PCR and western blotting. Age-and gender-matched wild-type (WT) littermates were used as controls. Cortical sirt3 localization was assessed using immunohistochemistry. The expression of sirt3 mRNA was significantly lower in the cortex of APP/PS1 double transgenic mice than in WT littermates (0.83 ± 0.24 vs. 1.10 ± 0.21, P < 0.05). A comparable reduction was found in sirt3 protein levels using western blotting. The ratio of mean optical density (MOD) of total sirt3/β-actin in the cortex was 0.77 ± 0.11 in APP/PS1 double transgenic mice and 1.34 ± 0.17 in the WT littermates (P < 0.01). Immunohistochemistry showed the same change as western blotting. The ratio of MOD of integral optical density/total area in APP/PS1 and WT littermates was 0.58 ± 0.02 and 0.71 ± 0.05 (P < 0.01). These data show that sirt3 was depleted in APP/PS1 double transgenic mice. The results suggest that mitochondrial sirt3 might participate in the development of AD via mitochondrial dysfunction.

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Section: Discussionmentioning

confidence: 71%

“…Animal Models APP/PS1 double transgenic mice (Jackson laboratory, stock number 004462) were purchased from model animal center of Nanjing University [12]. Eight (six females, two males) of APP/PS1 double transgenic mice (APP/PS1 group) aged 12 months were used as the experimental group.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

et al. 2015

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Imbalance of Microglial TLR4/TREM2 in LPS-Treated APP/PS1 Transgenic Mice: A Potential Link Between Alzheimer’s Disease and Systemic Inflammation

Zhou

Zhang

et al. 2019

Neurochem Res

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Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer’s Disease

Martins

Rivers-Auty

Allan

et al. 2016

JAD

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Obesity is associated with impaired memory in humans, and obesity induced by high-fat diets leads to cognitive deficits in rodents and in mouse models of Alzheimer’s disease (AD). However, it remains unclear how high-fat diets contribute to memory impairment. Therefore, we tested the effect of a high-fat diet on memory in male and female control non-transgenic (Non-Tg) and triple-transgenic AD (3xTgAD) mice and determined if a high-fat diet caused similar ultrastructural abnormalities to those observed in AD. Behavior was assessed in mice on control or high-fat diet at 4, 8, or 14 months of age and ultrastructural analysis at 8 months of age. A high-fat diet increased body weight, fat weight, and insulin levels with some differences in these metabolic responses observed between Non-Tg and 3xTgAD mice. In both sexes, high-fat feeding caused memory impairments in Non-Tg mice and accelerated memory deficits in 3xTgAD mice. In 3xTgAD mice, changes in hippocampal mitochondrial morphology were observed in capillaries and brain neuropil that were accompanied by a reduction in synapse number. A high-fat diet also caused mitochondria abnormalities and a reduction in synapse number in Non-Tg mice, but did not exacerbate the changes seen in 3xTgAD mice. Our data demonstrate that a high-fat diet affected memory in Non-Tg mice and produced similar impairments in mitochondrial morphology and synapse number comparable to those seen in AD mice, suggesting that the detrimental effects of a high-fat diet on memory might be due to changes in mitochondrial morphology leading to a reduction in synaptic number.

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Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

Cited by 3 publications

References 60 publications

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

Imbalance of Microglial TLR4/TREM2 in LPS-Treated APP/PS1 Transgenic Mice: A Potential Link Between Alzheimer’s Disease and Systemic Inflammation

Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer’s Disease

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