Dataset Information

Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.

ABSTRACT:

Background

Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.

Objective

The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD).

Methods

A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3-4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess long term effects of CD on the AD phenotype, animals were re-entrained to a no disruption (ND) schedule just prior to the endpoint, after which a Morris water maze (MWM) was used to assess spatial learning and memory.

Results

Dampening of nighttime activity levels occurred in disrupted animals, and female animals demonstrated a greater adaptability to CD. Diminished arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) levels in the suprachiasmatic nucleus (SCN) of 12-month male AβPP/PS1 exposed to the CD paradigm were observed, potentially accounting for the diminished re-entrainment response. Similarly, CD worsened performance in the MWM in 12-month male AβPP/PS1 animals, whereas no effect was seen in females.

Conclusions

Collectively, these findings show that exposure to chronic CD impairs circadian behavioral patterns and cognitive phenotypes of AβPP/PS1 mouse model in a sex-dependent manner.

SUBMITTER: Britz J

PROVIDER: S-EPMC10860643 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.

Britz Jesse J Ojo Emmanuel E Haque Nazmul N Dhukhwa Asmita A Hascup Erin R ER Hascup Kevin N KN Tischkau Shelley A SA

Journal of Alzheimer's disease : JAD 20240101 2

<h4>Background</h4>Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.<h4>Objective</h4>The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD).<h4>Methods</h4>A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activ ...[more]

PMID: 38143343

Similar Datasets

Project description:The symptomologies of Alzheimer's disease (AD) develop over decades suggesting modifiable lifestyle factors may contribute to disease pathogenesis. In humans, hyperinsulinemia associated with type 2 diabetes mellitus increases the risk for developing AD and both diseases share similar age-related etiologies including amyloidogenesis. Since we have demonstrated that soluble Aβ42 elicits glutamate release, we wanted to understand how diet-induced insulin resistance alters hippocampal glutamate dynamics, which are important for memory formation and consolidation. Eight to twelve-week-old C57BL/6J and AβPP/PS1 mice were placed on either a low-fat diet or high-fat diet (HFD) for 8 months. A HFD led to significant weight increases as well as impaired insulin sensitivity, glucose tolerance, and learning in both C57BL/6J and AβPP/PS1 mice. AβPP/PS1 low-fat diet mice had elevated hippocampal basal as well as stimulus-evoked glutamate release that was further increased with consumption of a HFD. Immunohistochemistry indicated an increase in vesicular glutamate transporter 1 and glial fibrillary acidic protein density in hippocampal subregions corresponding with this elevated extracellular glutamate. While no differences in hippocampal plaque load were observed, the elevated astrogliotic response surrounding the plaques in AβPP/PS1 HFD mice may have been a compensatory mechanism to control plaque accumulation. These data support that AβPP/PS1 mice have chronically elevated extracellular glutamate that is exacerbated by a HFD and that modifiable lifestyle factors such as obesity-induced insulin resistance can contribute to AD pathogenesis. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* and for *Open Data* because it made the data publicly available. The data can be accessed at https://osf.io/5whvu (figures for data) and https://osf.io/gd5vf (materials and methods). The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14490.

Dataset Information

Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.

Background

Objective

Methods

Results

Conclusions

Publications

Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.

Similar Datasets

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