Trent Wallis ¹, William A. Bubb ¹, James A. McQuillan ¹, Vladimir J. Balcar ² & Caroline Rae ¹

1 Discipline of Biochemistry, School of Molecular and Microbial Biosciences, The University of Sydney, NSW, 2006, Australia, ² Dept of Anatomy and Histology, The University of Sydney, NSW, 2006, Australia

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Methods

3.1. Materials

3.2. Mice

3.3. Real-time PCR analysis of differential gene expression

3.4. Uptake of 2-deoxyglucose by brain tissue prisms

3.5. Cerebral metabolism of D-[1-¹³C]glucose

4. Results

4.1. Gene expression in mdx vs control brain

4.1.1. Glucose transporter

4.1.2. Neurotransmitter receptors

4.1.3. Bioenergetics

4.1.4. Structural proteins

4.2. Age-related changes in gene expression

4.2.1. Glucose transporter

4.2.2. Neurotransmitter receptors

4.2.3. Bioenergetics

4.2.4. Structural proteins

4.3. 2-Deoxy-D-[1-¹⁴C]glucose uptake

4.4. Cerebral metabolism of D-[1-¹³C]glucose

5. Discussion

5.1. Glucose transporter expression and glucose use

5.2. Neurotransmitter receptor expression

5.3. Brain bioenergetics

5.4. Structural protein expression

5.5. Summary

6. Acknowledgements

7. References

1. ABSTRACT

Lack of expression of a single gene, dystrophin, causes the severe, progressive muscle wasting and mental deficits characteristic of Duchenne muscular dystrophy. In this work, we investigated the impact of dystrophin deletion on expression of other genes in the brain cortex, hippocampus and cerebellum using the murine homologue, the mdx mouse, and RT-PCR.

Expression of the brain glucose transporters GLUT1 and GLUT2 was found to be decreased, as were some subunits of the GABA_A and nicotinic acetylcholine receptors. Genes involved in bioenergetic homeostasis, such as the mitochondrial creatine kinase and the gamma subunit of ATP synthase were also found to be abnormally expressed, while expression of the structural proteins beta-dystrobrevin and rapsyn was also significantly affected.