Age-Related Increase of Insulin-Degrading Enzyme Is Inversely Correlated with Cognitive Function in APPswe/PS1dE9 Mice

Zhang, Yi; Wang, Peichang

doi:10.12659/msm.909596

Cited by 10 publications

(4 citation statements)

References 40 publications

(43 reference statements)

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“…Cognitive impairment is often manifested as the impairment of one or more abilities related to perception, attention, memory, and thinking [6]. Over 46 million older adults suffer from cognitive impairment, which imposes a heavy burden on families and society [7,8]. Moreover, the cumulative dementia incidence rate is 14.9% in older adults with mild cognitive impairment aged above 65 years [9].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Association Between Depressive Symptoms and Cognitive Function Among Older Adults: A Latent Growth Curve Modeling Approach

Gao

Liu

et al. 2022

Int J Public Health

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Objectives: Although the evidence from numerous longitudinal studies has indicated a remarkable change in cognitive function (CF) and depressive symptoms (DS) over time, the parallel latent growth curve model (LGCM) has seldom been used to simultaneously investigate the relationship between their change trajectories. This study aimed to examine whether a change in DS was associated with CF over time using an LGCM.Methods: Data were collected from the Chinese Longitudinal Healthy Longevity Survey’s 2011, 2014, and 2018 waves. A parallel LGCM examined the association between CF and DS.Results: The multivariate conditioned model’s goodness of fit supported the validity of the longitudinal model (Tucker-Lewis index [TLI] = 0.90, comparative fit index [CFI] = 0.96, root mean square error of approximation [RMSEA] = 0.04). The results showed that the CF intercept was positively to the DS slope (β = 0.42, p = 0.004). The CF and DS slopes were significantly linked (β = −0.65, p = 0.002).Conclusion: The findings expand the knowledge about CF’s effect on DS in older adults.

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Section: Introductionmentioning

confidence: 99%

Longitudinal Association Between Depressive Symptoms and Cognitive Function Among Older Adults: A Latent Growth Curve Modeling Approach

Gao

Liu

et al. 2022

Int J Public Health

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“…Based on some studies, the age in C57BL/6 J mice may be divided into the following stages: 21-60 days of age (adolescence), 3-6 months of age (adult age), 10-15 months of age (middle age) and 18-24 months of age (old age). 18,26 The SPA and feeding behavior were measured daily on a per cage basis. At the end of the experiment, 10 animals of each group (SSD, n ¼ 10 and LSD, n ¼ 10) were used for the determination of body composition (visceral fat depots and brown adipose tissue, as well as water, fat mass and fat-free mass of carcass).…”

Section: Methodsmentioning

confidence: 99%

Early-life mice housed in standard stocking density reduce the spontaneous physical activity and increase visceral fat deposition before reaching adulthood

et al. 2022

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Laboratory rodents spend the entire day housed in standard cages that provide a restricted area for movements and might, therefore, limit physical activity. However, it has not been tested in immature rodents of ages ranging from weaning to adulthood (adolescence period) whether the restricted area per animal does actually reduce physical activity and impact the body composition. We analyzed the spontaneous physical activity and feeding behavior during the adolescence of mice kept in two different housing conditions (standard stocking density (SSD) versus low stocking density (LSD)). We aimed to compare the body composition between SSD and LSD groups before they reached adulthood. Differential housing began at four weeks of age and was maintained for four weeks until euthanasia at eight weeks of age. The SSD group had a floor space of 88 cm2 available per animal, while LSD mice were housed with a floor space of 320 cm2 per animal, increasing the individual radius for movement more than three-fold compared with standard requirements. Mice kept in SSD exhibit lower spontaneous physical activity than mice kept in LSD. Early-life exposure to reduced physical activity in mice housed in SSD resulted in greater visceral fat accumulation before adulthood. An environment enabling/stimulating physical activity should be established for rodents as early as possible. This study will be helpful in showing that mice kept in SSD are early exposed to a reduced physical activity already in the adolescence period. Our findings could raise reflections about the translatability of rodents kept in SSD to healthy active humans.

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“…Hdac4, encoding a histone deacetylase and a recognized regulator of cellular senescence (Di Giorgio et al, 2021), was significantly reduced in aged astrocytes and ependymal cells. Meanwhile, the Insulin-degrading enzyme (IDE), a key factor involved in amyloid-beta clearance (Zhang and Wang, 2018), showed increased expression mostly in subtypes of neurons, including interneurons, OB neurons, interbrain, and midbrain neurons. While many of these genes have been previously reported to be associated with aging, our analysis represents the first global view of their alterations across over 300 subtypes.…”

Section: Introductionmentioning

confidence: 99%

A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in the human and mouse brains

Sziraki

Lee

et al. 2022

Preprint

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Although several studies have applied single-cell approaches to explore gene expression changes in aged brains, they were limited by the relatively shallow sampling of brain cell populations, and thus may have failed to capture aspects of the molecular signatures and dynamics of rare cell types associated with aging and diseases. Here, we set out to investigate the age-dependent dynamics of transcription and chromatin accessibility across diverse brain cell types. With EasySci, an extensively improved single-cell combinatorial indexing strategy, we profiled ~1.5 million single-cell transcriptomes and ~400,000 single-cell chromatin accessibility profiles across mouse brains spanning different ages, genotypes, and both sexes. With a novel computational framework designed for characterizing cellular subtypes based on the expression of both genes and exons, we identified > 300 cell subtypes and deciphered the underlying molecular programs and spatial locations of rare cell types (e.g., pinealocytes, tanycytes) and subtypes. Leveraging these data, we generate a global readout of age-dependent cell population dynamics with high cellular subtype resolution, providing insights into cell types that expand (e.g., rare astrocytes and vascular leptomeningeal cells in the olfactory bulb, reactive microglia and oligodendrocytes) or are depleted (e.g., neuronal progenitors, neuroblasts, committed oligodendrocyte precursors) as age progresses. Furthermore, we explored cell-type-specific responses to genetic perturbations associated with Alzheimer's disease (AD) and identify rare cell types depleted (e.g., mt-Cytb+, mt-Rnr2+ choroid plexus epithelial cells) or enriched (e.g., Col25a1+, Ndrg1+ interbrain and midbrain neurons) in both AD models. Key findings are consistent between males and females, validated across the transcriptome, chromatin accessibility, and spatial analyses. Finally, we profiled a total of 118,240 single-nuclei transcriptomes from twenty-four human brain samples derived from control and AD patients, revealing highly cell-type-specific and region-specific gene expression changes associated with AD pathogenesis. Critical AD-associated gene signatures were validated in both human and mice. In summary, these data comprise a rich resource for exploring cell-type-specific dynamics and the underlying molecular mechanisms in both normal and pathological mammalian aging.

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Age-Related Increase of Insulin-Degrading Enzyme Is Inversely Correlated with Cognitive Function in APPswe/PS1dE9 Mice

Cited by 10 publications

References 40 publications

Longitudinal Association Between Depressive Symptoms and Cognitive Function Among Older Adults: A Latent Growth Curve Modeling Approach

Longitudinal Association Between Depressive Symptoms and Cognitive Function Among Older Adults: A Latent Growth Curve Modeling Approach

Early-life mice housed in standard stocking density reduce the spontaneous physical activity and increase visceral fat deposition before reaching adulthood

A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in the human and mouse brains

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