# Sleep deprivation elevates, and sleep alleviates, oxidative stress in the brain.

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2021 · $328,140

## Abstract

Abstract
For reasons that remain unknown, sleep is essential for the reversal of deficits in cognition and performance
that accumulate with increased severity during protracted wake. One of the most robust and reliable
features of sleep is a reduction of cerebral metabolism, manifested by a decline in brain temperature and a
decline in brain glucose and oxygen utilization, relative to wake. It stands to reason that the metabolic down
state is essential for the restorative function of sleep, yet the biochemical basis for this relationship is
uncertain. Oxidative metabolism of glucose fuels neuronal activity. Postmortem assays indicate that
protracted wake produces an accumulation of oxidative stress in the brain. We hypothesize that reduced
glucose utilization in sleep reverses a metabolically-driven shift in the redox status (the balance of
oxidation and reduction reactions) of parvalbumin-positive neurons caused by the high metabolic
demand of these cells in the waking brain. We further hypothesize that this function of sleep is
facilitated in part by an extracellular matrix structure known as perineuronal nets, which serve to
buffer against oxidative stress in metabolically vulnerable neurons. To address these hypotheses, we
will perform a systemic pharmacological manipulations (the oxidation/reduction reaction substrate nicotinic
adenine dinucleotide) known to affect the brain’s capacity to withstand oxidative stress. We will also assess
perform brain region-specific depletion of perineuronal nets. We will assess the effects of these
manipulations, and those of sleep/wake cycle manipulations, on cellular redox status markers, both in real-
time in vivo using intravital microscopy, and post mortem by coupling oxidation assays with cell type-specific
immunochemical markers and histochemical assessment of perineuronal net intensity. We will additionally
measure the effects of the experimental manipulations on electroencephalographic markers for brain fatigue
and sleep need. The anticipated results will establish a causal interrelationship between sleep/wake cycles
and brain redox status, and will identify brain oxidation/reduction reactions as a target for both diagnostic
inquiry and therapeutic intervention in the face of sleep insufficiency.
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## Key facts

- **NIH application ID:** 10118229
- **Project number:** 5R01NS078498-08
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Jonathan P Wisor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,140
- **Award type:** 5
- **Project period:** 2012-02-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118229

## Citation

> US National Institutes of Health, RePORTER application 10118229, Sleep deprivation elevates, and sleep alleviates, oxidative stress in the brain. (5R01NS078498-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10118229. Licensed CC0.

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