Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged APP/PS1 Mice

Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; Xiao, Na; Hu, Gang; Xiao, Ming

doi:10.1093/ijnp/pyu116

Cited by 69 publications

(65 citation statements)

References 76 publications

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“…APP/PS1 transgenic mice expressing mutant human APP and PS1 genes are a useful research tool to study Aβ-related pathogenesis. There are several studies characterizing cognitive as well as noncognitive abnormality in APP/PS1 mice at 15-24 months of age (Morgan et al 2000;Arendash et al 2001;Sadowski et al 2004;Wilcock et al 2004;Hooijmans et al 2007;Minkeviciene et al 2008;Pistell et al 2008;Mei et al 2010;Ke et al 2011;Gengler et al 2012;Manczak and Reddy 2012;Wang et al 2012;Duffy and Hölscher 2013;Do et al 2014;Huang et al 2015;Janus et al 2015;Sahlholm et al 2015;Yousefi et al 2015) (A detailed summary is available in Table 2). However, the majority of experiments utilize young or adult APP/PS1 mice, which does not replicate typical hallmarks of AD, such as severe hippocampal atrophy and extensive neuronal loss (Bales 2012;Bilkei-Gorzo 2014).…”

Section: Discussionmentioning

confidence: 99%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/ PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

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Section: Discussionmentioning

confidence: 99%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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“…Behavioural symptoms in the APP/PS1 mouse model, which are correlated to neuropsychological clinical symptoms, include disturbances in locomotor activity [34], anxiety [35, 36], aggression, and social behaviour [37–39]. The present study thus focuses on performance in OF and EPM tests, in which animals are allowed to explore the environment undisturbed, and where different behavioural parameters can be assessed, and on the SI test, where interest to engage into social interaction is analysed.…”

Section: Discussionmentioning

confidence: 99%

Behavioural Phenotyping of APPswe/PS1δE9 Mice: Age-Rrelated Changes and Effect of Long-Term Paroxetine Treatment

et al. 2016

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Alzheimer’s disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset of cognitive symptoms both in humans with early and late onset AD. The behavioural profile promoted by the AD pathology is believed to associate with degeneration of the serotonergic system. Using the APPswe/PS1δE9 model of AD-like pathology starting with 9 months old mice, we characterised long term non-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests. Long-term treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine was applied to assess the role of 5-HT on the behavioural profile; duration of treatment was 9 months, initiated when mice were 9 months of age. Treatment with paroxetine delays the decline in locomotion, in exploration and risk assessment behaviour, found in the APP/PS1 mice. APP/PS1 mice also exhibit low social activity and less aggressiveness, both of which are not affected by treatment with paroxetine. The APP/PS1 behavioural phenotype, demonstrated in this study, only begins to manifest itself from 12 months of age. Our results indicate that treatment with SSRI might ameliorate some of the behavioural deficits found in aged APP/PS1 mice.

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“…SI was shown to exacerbate the impairment of spatial working memory and the accumulation of Aβ42 in adult APP/PS1 mice (Huang, Liang, Ke, Chang & Hsieh-Li, 2011). In seventeen-month-old APP/PS1 mice these effects are even more pronounced, and isolation housing was found to decrease learning, memory functions and exploratory behaviour, and exacerbate AD pathology such as accumulation of Aβ and hippocampal volume loss (Huang et al, 2015). However, no study looked at the effects of SI on emotionality and social behaviours in APP/PS1 mice.…”

Section: Introductionmentioning

confidence: 97%

Social isolation impacts late-life socio-cognitive decline in APP/PS1 mice

Rens

D’Hooge

Jeugd

2019

Preprint

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In this study the effects of social isolation (SI) were investigated in APP/PS1 mice. It was found that SI during adolescence has an impact on anxiogenic behaviour, such that isolated animals tend to explore a threatening environment less than non-isolated animals as assessed with the EPM test, and that this holds for both AD and non-AD mice. While no evidence was found for any differences in short-term memory as assessed by the Y-maze, long-term memory seemed to be affected in a context-dependent manner. Object memory as assessed with the NOR test was affected in APP/PS1 mice compared to WT mice, but this deficit was not induced or influenced by SI. When it comes to social recognition memory however, we found that SI exacerbated the social memory deficit in AD mice, and even induced a deficit in WTs. Associative fear memory as assessed with the PA test suggested that WTs perform better when group housed, and APP/PS1 mice better when socially isolated. The link between isolation and AD, or cognition in general, may be more complex than initially thought. The effect of isolation may not be the same for AD versus non-AD subjects.

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Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged APP/PS1 Mice

Cited by 69 publications

References 76 publications

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Behavioural Phenotyping of APPswe/PS1δE9 Mice: Age-Rrelated Changes and Effect of Long-Term Paroxetine Treatment

Social isolation impacts late-life socio-cognitive decline in APP/PS1 mice

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