Reduction of the molecular chaperone binding immunoglobulin protein (BiP) accentuates the effect of aging on sleep-wake behavior

Neurobiology of Aging
Nirinjini NaidooAllan I Pack

Abstract

Sleep and wake quality, quantity, and architecture become modified with aging. Sleep and wake quality decline coinciding with increased fragmentation of both states across aging. We have previously shown that this age-related decline in sleep-wake quality is associated with increased endoplasmic reticular (ER) stress and decreased expression of the major ER chaperone binding immunoglobulin protein (BiP). BiP, also known as glucose-regulated protein 78, plays a key role in controlling the cellular response to ER stress, acting as a regulator of a protein homeostatic signaling pathway known as the unfolded protein response. Induction of BiP during cellular stress is part of an adaptive prosurvival mechanism. Here, using mice heterozygous for BiP, we investigated the effect of reduced BiP expression on sleep-wake behavior across aging; complete knockdown of BiP is embryonic lethal. We report that BiP heterozygosity accentuates the aging sleep-wake phenotype. Sleep and wake fragmentation was more pronounced in the BiP heterozygotes across the 3 ages examined. In mice lacking 1 functional copy of BiP, we observed an age-related significant reduction in wake bout duration and increase in wake bout numbers during the active period, as...Continue Reading

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Citations

Nov 1, 2020·Aging Cell·Rebecca C Taylor, Claudio Hetz
May 30, 2020·Current Opinion in Physiology·Laura E McKillop, Vladyslav V Vyazovskiy

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