# Deficient Neuronal Glucose Transport Underlies Cortical Hyperexcitability in Mouse Models of Huntington’s Disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $195,000

## Abstract

ABSTRACT
Glucose is the main and preferred energy substrate in the brain. In resting conditions, glucose is taken up into
neurons by the glucose transporter 3 (GLUT3). However, in Huntington’s disease (HD), a genetic, fatal,
neurodegenerative disorder caused by a mutation in the Huntingtin gene and characterized by abnormal
movements, as well as cognitive and psychiatric symptoms, brain energy metabolism and GLUT3 expression
are significantly reduced. Recent studies by our group and others also emphasize the presence of a
neurodevelopmental component in HD. In particular, we have reported structural abnormalities in the cerebral
cortex of HD model mice, which are reminiscent of malformations of cortical development. We hypothesize that
in HD, GLUT3 deficits cause abnormal brain development leading to cortical hyperexcitability and progressive
emergence of symptoms. The present proposal is designed to examine, in juvenile and adult-onset mouse
models of HD, the role of GLUT3 in cortical development and, if proven deficient, to reverse this deficiency and
prevent development of the phenotype. There are two specific aims: Aim 1 will examine, primarily, GLUT3
expression in developing HD mice, from embryonic to adult stages. Aim 2 will use genetic strategies to explore
how under- or over-expression of GLUT3 affects the development of disease progression. We have generated
and characterized GLUT3-deficient mouse models, and for this project we will create a new line of GLUT3
overexpressing mice, which will be crossed with HD mice. We expect to see an improvement of HD symptoms
in mice with overexpression of GLUT3 in cortical neurons. Specific readouts include molecular, behavioral, and
electrophysiological techniques, of which our laboratories are very well-versed. This project is innovative as the
role of glucose transport in HD has been underexplored, particularly during brain development. It is also highly
significant as discovering new strategies to improve glucose transport into the brain during early development
could be beneficial and hopefully prophylactic.

## Key facts

- **NIH application ID:** 10452907
- **Project number:** 1R21NS123883-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Carlos T Cepeda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452907

## Citation

> US National Institutes of Health, RePORTER application 10452907, Deficient Neuronal Glucose Transport Underlies Cortical Hyperexcitability in Mouse Models of Huntington’s Disease (1R21NS123883-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10452907. Licensed CC0.

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