Endoplasmic Reticulum Stress in Wake-active Neurons Progresses with Aging

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2011 Mar 11

PMID 21388495

Citations 40

Authors

Nirinjini Naidoo

Jingxu Zhu

Yan Zhu

Polina Fenik

Jie Lian

Ray Galante

Sigrid Veasey

Affiliations

Soon will be listed here.

Abstract

Fragmentation of wakefulness and sleep are expected outcomes of advanced aging. We hypothesize that wake neurons develop endoplasmic reticulum dyshomeostasis with aging, in parallel with impaired wakefulness. In this series of experiments, we sought to more fully characterize age-related changes in wakefulness and then, in relevant wake neuronal populations, explore functionality and endoplasmic reticulum homeostasis. We report that old mice show greater sleep/wake transitions in the active period with markedly shortened wake periods, shortened latencies to sleep, and less wake time in the subjective day in response to a novel social encounter. Consistent with sleep/wake instability and reduced social encounter wakefulness, orexinergic and noradrenergic wake neurons in aged mice show reduced c-fos response to wakefulness and endoplasmic reticulum dyshomeostasis with increased nuclear translocation of CHOP and GADD34. We have identified an age-related unfolded protein response injury to and dysfunction of wake neurons. It is anticipated that these changes contribute to sleep/wake fragmentation and cognitive impairment in aging.

Citing Articles

Biology of Stress Responses in Aging.

Maragkakis M, Malla S, Hatzoglou M, Trifunovic A, Glick A, Finkel T Aging Biol. 2024; 1.

PMID: 38500537 PMC: 10947073. DOI: 10.59368/agingbio.20230001.

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.

Chen X, Shi C, He M, Xiong S, Xia X Signal Transduct Target Ther. 2023; 8(1):352.

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Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.

Morrone C, Raghuraman R, Hussaini S, Yu W Mol Neurodegener. 2023; 18(1):27.

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Kroeger D, Vetrivelan R Aging Brain. 2023; 3:100068.

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Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging.

Cabral-Miranda F, Tamburini G, Martinez G, Ardiles A, Medinas D, Gerakis Y EMBO J. 2022; 41(22):e111952.

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