Abnormal circadian locomotor rhythms and Per gene expression in six-month-old triple transgenic mice model of Alzheimer’s disease

Wu, Mei‐Na; Zhou, Fang; Cao, Xiuli; Yang, Junting; Bai, Yueyu; Yan, Xudong; Cao, Ji‐Min; Qi, Jin-Shun

doi:10.1016/j.neulet.2018.04.008

Cited by 29 publications

(17 citation statements)

References 26 publications

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“…Activity in AD mice in our sample was lower than that of the WT mice in the early part of the night cycle at both 3.5 months and 7 months. This lowered activity in AD mice is in agreement with Wu et al (2018) who used the 3xTg-AD mouse, containing mutations in amyloid, tau, and the PS1 gene, and found that AD mice had lower total daily activity in running compared to WT mice.…”

Section: Discussionsupporting

confidence: 89%

“…These differences were significant in the Wt mice and similar patterns of activity were seen amongst the other conditions (dual Tg and tau), although not statistically significant (Figures 3B,C). Wu et al (2018) showed similar results, in that the total daily activity in female mice was greater than that of male mice, regardless of genotype (WT v. 3xTg-AD). While Wu et al (2018) tested at 6 months of age, we saw these differences at an early testing age; at 3.5 months; however, the differences were less in the transgenic mice than in the Wt mice.…”

Section: Sex Differencessupporting

confidence: 56%

“…This mouse model may be suitable for future daily activity rhythm analysis since wheel-running activity was disrupted early on; others have assessed wheel running in AD mice at later ages (Duncan et al, 2012;Boggs et al, 2017;Craven et al, 2018;Wu et al, 2018). Further analysis showed that the activity of the Wt mice did not vary significantly with age, zinc administration, or sex; however, these variables did affect both the tau and dual Tg mice, with the dual Tg mice being the most affected, particularly with respect to zinc administration.…”

Section: Discussionmentioning

confidence: 99%

“…Mouse models assessing circadian rhythms and sleep solely in male mice, have shown that age can impact sleep and wheel running activity in non-Tg inbred mouse strains (Valentinuzzi et al, 1997;Hasan et al, 2012). The 3xTg-AD mouse model showed altered circadian locomotor rhythms (Wu et al, 2018) with female mice showing less disruptions compared to males. Female 3xTgAD mice have also been found to be less active than non-Tg mice during the evening (lights-off) period (Sterniczuk et al, 2010).…”

Section: Sex Differencesmentioning

confidence: 99%

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Wheel-Running Behavior Is Negatively Impacted by Zinc Administration in a Novel Dual Transgenic Mouse Model of AD

et al. 2020

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Alzheimer's disease (AD) is a neurocognitive disorder that impacts both the brain and behavior. Metal ions, including zinc (Zn), have been seen to play an important role in AD-related pathology. In this study, we show alterations in wheel-running behavior both early and late in disease progression in a novel dual Tg mouse model of AD. This mouse includes both amyloid and tau pathology through its cross with the J20 (hAPP) and P301L (Tau) parentage. Animals were given either lab water or water that had been supplemented with 10 ppm Zn. Wheel running was assessed through individually housing mice and measuring wheel-running activity in both the light and dark cycles. Dual Tg mice showed significantly less activity in the first part of the dark cycle than WT mice at both 3.5 and 7 months of age (p < 0.05). Dual Tg mice given Zn water showed less activity compared to dual Tg mice on lab water, tau mice on Zn water, or WT mice given either lab or Zn water (p < 0.05) at 7 months. Female mice in this study consistently showed higher activity compared to male mice in all groups whereas Zn led to reduced activity. Daily activity rhythm was altered in both the tau and dual Tg mice, and Zn impacted this alteration through effects on amyloid, tau, and through circadian pathways.

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Section: Discussionsupporting

confidence: 89%

Section: Sex Differencessupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Sex Differencesmentioning

confidence: 99%

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Wheel-Running Behavior Is Negatively Impacted by Zinc Administration in a Novel Dual Transgenic Mouse Model of AD

et al. 2020

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“…Alterations in the circadian rhythm, including sleep disorders, have been implicated in the development of neurodegenerative disorders, including AD (Hood and Amir, 2017;Wall et al, 2018). Circadian alterations and decreased expression of PER2 have been reported in brain of transgenic model of AD (Wu et al, 2018), and it would be interesting to examine sleep behavior in calpain-1 KO mice. Expression of ARC was relatively low in both WT and calpain-1 KO mice, and while we detected a significant difference in the overall brain levels of ARC, there was no significant differences in ARC levels in hippocampus or cortex.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer’s Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain

Zhou

Wang

et al. 2020

Front. Genet.

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Calpains represent a family of calcium-dependent proteases participating in a multitude of functions under physiological or pathological conditions. Calpain-1 is one of the most studied members of the family, is ubiquitously distributed in organs and tissues, and has been shown to be involved in synaptic plasticity and neuroprotection in mammalian brain. Calpain-1 deletion results in a number of phenotypic alterations. While some of these alterations can be explained by the acute functions of calpain-1, the present study was directed at studying alterations in gene expression that could also account for these phenotypic modifications. RNA-seq analysis identified 354 differentially expressed genes (DEGs) in brain of calpain-1 knock-out mice, as compared to their wild-type strain. Most DEGs were classified in 10 KEGG pathways, with the highest representations in Protein Processing in Endoplasmic Reticulum, MAP kinase and Alzheimer's disease pathways. Most DEGs were down-regulated and validation of a number of these genes indicated a corresponding decreased expression of their encoded proteins. The results indicate that calpain-1 is involved in the regulation of a significant number of genes affecting multiple brain functions. They also indicate that mutations in calpain-1 are likely to be involved in a number of brain disorders.

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Circadian rhythmicity of amyloid‐beta‐related molecules is disrupted in the choroid plexus of a female Alzheimer's disease mouse model

Furtado

Esgalhado

Duarte

et al. 2022

J of Neuroscience Research

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The choroid plexus (CP) is part of the blood‐cerebrospinal fluid barrier (BCSFB) and was recently described as an important component of the circadian clock system. It is the principal source of cerebrospinal fluid (CSF) and responsible for the synthesis and secretion of various neuroprotective peptides including those involved in amyloid‐β (Aβ) transport/degradation, contributing to Aβ homeostasis. Inadequate Aβ metabolic clearance and transport across the BCSFB have been associated with circadian dysfunctions in Alzheimer's disease (AD) patients. To investigate whether AD pathology influences Aβ scavengers circadian expression, we collected CP at different time points from an AD mouse model (APP/PS1) (female and male animals, aged 6‐ and 12‐months‐old) and analyzed their mRNA expression by Real‐time RT‐PCR. Only angiotensin‐converting enzyme (Ace) expression in 6‐month‐old female wild‐type mice and transthyretin (Ttr) expression in 12‐month‐old female wild‐type mice presented significant rhythmicity. The circadian rhythmicity of Ace and Ttr, prompt us to analyze the involvement of circadian rhythm in Aβ uptake. A human CP papilloma (HIBCPP) cell line was incubated with Aβ‐488 and uptake was evaluated at different time points using flow cytometry. Aβ uptake displayed circadian rhythmicity. Our results suggest that AD might affect Aβ scavengers rhythmicity and that Aβ clearance is a rhythmic process possibly regulated by the rhythmic expression of Aβ scavengers.

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Abnormal circadian locomotor rhythms and Per gene expression in six-month-old triple transgenic mice model of Alzheimer’s disease

Cited by 29 publications

References 26 publications

Wheel-Running Behavior Is Negatively Impacted by Zinc Administration in a Novel Dual Transgenic Mouse Model of AD

Wheel-Running Behavior Is Negatively Impacted by Zinc Administration in a Novel Dual Transgenic Mouse Model of AD

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer’s Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain

Circadian rhythmicity of amyloid‐beta‐related molecules is disrupted in the choroid plexus of a female Alzheimer's disease mouse model

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