# High throughput marker for cognitive deficit: cellular autofluorescence

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $491,178

## Abstract

ABSTRACT
For the past decade, several lines of evidence have shown a direct role for oxidative stress in the pathology of
schizophrenia (SZ). Although peripheral changes associated with oxidative stress may be useful to establish
biomarkers for the disease, connecting such peripheral changes to brain dysfunction has not yet been fully
established. Furthermore, there is a need to develop high throughput assays for measuring such peripheral
changes. We recently found that oxidative stress-associated endogenous autofluorescence (AF) is aberrantly
augmented in SZ cells. AF is regulated by the GAPDH stress cascade, and the extent of AF is negatively
correlated with cognitive flexibility evaluated by the Wisconsin Card Sorting Test. Meanwhile, we have recently
found that the selectively activated GAPDH stress cascade in microglia in the prefrontal cortex is likely to
mediate cognitive inflexibility in an oxidative stress-associated mouse model. We have observed that
expression of Cd11b (a key factor for microglia to target to synapse) is regulated by the GAPDH stress
cascade in this mouse model. Based on these promising preliminary data, we hypothesize that activation of the
GAPDH stress cascade and associated altered AF triggers pathological changes in microglia, which in turn
affects synaptic connectivity in the prefrontal cortex that underlies cognitive flexibility. To address this
hypothesis, we propose the following three aims: 1) to establish a high throughput assay that measures cellular
AF from human blood samples; 2) to identify specific cognitive domain(s) that is correlated with and predicted
by augmented AF in blood cells; and 3) to identify a molecular mechanism by which the GAPDH stress
cascade mediates cognitive inflexibility in an oxidative stress-associated animal model. Through these three
Aims, we seek the translational potential of intervening in the GAPDH stress cascade to ameliorate cognitive
deficits by using AF in blood cells as an objective high throughput marker.

## Key facts

- **NIH application ID:** 10093131
- **Project number:** 5R01MH107730-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Akira Sawa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $491,178
- **Award type:** 5
- **Project period:** 2018-04-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093131

## Citation

> US National Institutes of Health, RePORTER application 10093131, High throughput marker for cognitive deficit: cellular autofluorescence (5R01MH107730-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093131. Licensed CC0.

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