# Kynurenic Acid, Sleep and Cognition

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2021 · $292,031

## Abstract

Poor sleep quality or disrupted sleep, due to reasons such as sleep disorders, psychiatric
disturbances, or aging, are associated with impairments in cognitive function. Deficits in
learning and memory that can result from disrupted sleep have recurring and profound impacts
on daily function. Understandably, unraveling the common molecular mechanisms between
sleep disturbances and neurocognitive impairments – which may lead to new therapeutic
approaches to alleviate these outcomes – is of great importance. Our project is designed to test
the overall hypothesis that kynurenic acid (KYNA), an astrocyte-derived metabolite of the
kynurenine pathway (KP) of tryptophan metabolism, represents a key molecular link between
sleep disturbances and cognitive dysfunction. We will examine, in rats, a) the mechanisms
linking sleep deprivation (SD) and increased KYNA formation; b) the role of KYNA in connecting
sleep dysfunction and cognitive deficits; and c) the therapeutic value of KYNA synthesis
inhibition to overcome cognitive deficits after SD. A newly developed specific inhibitor of
kynurenine aminotransferase II (KAT II), the main enzyme responsible for KYNA formation, will
be used as an experimental tool to mechanistically test the hypothesis. There are three specific
aims to test our hypothesis. Aim #1: To examine the dynamics of KP metabolism in the brain,
liver, and blood after SD. Working hypothesis: Peripheral changes in kynurenine pathway
metabolism drive increased KYNA formation in the hippocampus after SD. Aim #2: To
investigate the impact of up- and down- regulation of KYNA formation on sleep architecture.
Working hypothesis: Elevations in KYNA adversely impact sleep and targeted inhibition of KAT
II can improve sleep quality. Aim #3: To evaluate the impact of KYNA synthesis inhibition in
attenuating hippocampal-mediated cognitive dysfunction and improving sleep quality after SD.
Working hypothesis: Inhibition of KAT II serves as an efficacious strategy to overcome sleep
loss-induced cognitive dysfunction. Successful completion of these experiments will define
causal relationships between KP metabolism, sleep disturbances, and hippocampal-mediated
cognitive functions. The proposed research will advance our understanding of common
molecular mechanisms between sleep disturbances and neurocognitive impairments, paving the
way for novel therapies to alleviate these outcomes.

## Key facts

- **NIH application ID:** 10123017
- **Project number:** 5R01NS102209-06
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Ana Pocivavsek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $292,031
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123017

## Citation

> US National Institutes of Health, RePORTER application 10123017, Kynurenic Acid, Sleep and Cognition (5R01NS102209-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123017. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*