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Published on: March 23, 2011
Endoplasmic reticulum stress in wake-active neurons progresses with aging
Nirinjini Naidoo1, Jingxu Zhu, Yan Zhu
1Division of Sleep Medicine, Center for Sleep & Circadian Neurobiology, School of Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, PA 19104, USA. naidoo@mail.med.upenn.edu
Aging Cell
|March 11, 2011
Summary
Aging disrupts sleep patterns, causing more frequent wake/sleep transitions and shorter wakefulness. This is linked to endoplasmic reticulum stress and dysfunction in key wake-promoting neurons.
Area of Science:
- Neuroscience
- Aging Research
- Sleep Science
Background:
- Sleep-wake fragmentation is common in aging.
- Aging may impair wakefulness by affecting neuronal endoplasmic reticulum homeostasis.
Purpose of the Study:
- To characterize age-related changes in sleep-wake patterns.
- To investigate the functionality and endoplasmic reticulum homeostasis of wake neurons in aging.
Main Methods:
- Studied sleep-wake behavior in aged mice.
- Examined orexinergic and noradrenergic wake neurons for c-fos response and endoplasmic reticulum markers (CHOP, GADD34).
Main Results:
- Old mice exhibited increased sleep/wake transitions, shorter wake periods, and reduced wakefulness during social encounters.
- Aged wake neurons showed diminished c-fos response and signs of endoplasmic reticulum stress, including increased CHOP and GADD34 nuclear translocation.
Conclusions:
- Identified age-related unfolded protein response injury and dysfunction in wake neurons.
- These neuronal changes likely contribute to sleep-wake fragmentation and cognitive decline in aging.
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