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

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2023 Dec 25

PMID 38143343

Authors

Jesse Britz

Emmanuel Ojo

Nazmul Haque

Asmita Dhukhwa

Erin R Hascup

Kevin N Hascup

Shelley A Tischkau

Affiliations

Soon will be listed here.

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.

Citing Articles

Lifespan of male and female APP/PS1 and APP mouse models of Alzheimer's disease.

Roberts H, Fang Y, Quinn K, Hill T, Peck M, Bartke A bioRxiv. 2024; .

PMID: 39464050 PMC: 11507819. DOI: 10.1101/2024.10.15.618508.

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