Myelin, copper, and the cuprizone model of schizophrenia

Nicole R. Herring, Christine Konradi

Departments of Pharmacology and Psychiatry and Center for Molecular Neuroscience and Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee, 37203

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Structure and function of oligodendrocytes

4. Myelin: a major player in cognition and intellectual performance

5. Evolution and ontogeny of myelin

5.1. Evolution of myelin

5.2. Embryonic development of oligodendrocytes and oligodendrocyte regeneration in the adult brain

6. Disorders of myelin

6.1. Typical demyelinating disorders: multiple sclerosis and leukodystrophies

6.2. White matter abnormalities in schizophrenia

6.2.1. Post-mortem and imaging studies show myelin abnormalities in schizophrenia

6.2.2. Microarray- and gene expression studies highlight myelin abnormalities in schizophrenia

6.2.3. Factors important for oligodendrocyte development and myelination are known to be affected in schizophrenia

6.2.3.1. Electrical activity

6.2.3.2. Glutamate

6.2.3.3. Neuregulin 1 (NRG1) and ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)

6.2.3.4. Disrupted in schizophrenia (Disc1)

6.2.3.5. Reelin (RELN)

6.2.3.6. Oligodendrocyte lineage transcription factor 2 (OLIG2)

6.2.3.7. Brain-derived neurotrophic factor (BDNF)

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6.3. White matter abnormalities in other psychiatric disorders

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6.3.1. Mood disorders

6.3.2. Drugs of abuse

7. Copper metabolism, the cuprizone model of demyelination, and their relevance to schizophrenia

7.1. Cuprizone and copper

7.1.1. Role of copper in the CNS

7.1.2. Genetic disorders of copper metabolism

7.1.3. Copper levels in schizophrenia

7.2. The cuprizone model of demyelination in the mouse

7.3. The cuprizone model of demyelination in the rat