Age-Related Increase in the Number of Oligodendrocytes Is Dysregulated in Schizophrenia and Mood Disorders

Victor Vostrikov,Natalya Uranova

doi:10.1155/2011/174689

Abstract

The postnatal maturation of the human prefrontal cortex is associated with substantial increase of number of oligodendrocytes. Previously, we reported decreased numerical density of oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. To gain further understanding of the role oligodendrocytes in pathogenesis of schizophrenia and mood disorders, we examined the effect of the age on the number of oligodendrocytes in the prefrontal cortex in schizophrenia, bipolar disorder, and major depressive disorder. We revealed the age-related increase in numerical density of oligodendrocytes in layer VI and adjacent white matter of BA10 and BA 9 in normal controls but not in schizophrenia, bipolar disorder, and major depressive disorder. The absence of normal increase in the number of oligodendrocytes in gray and white matter with age in schizophrenia and mood disorders suggests that age-related process of oligodendrocyte increase is dysregulated in schizophrenia and mood disorders.

Highlights

Disconnection among different brain regions is believed to contribute to the abnormal functioning of neural networks and has been postulated to be central to the pathophysiology of schizophrenia [1,2,3]
As oligodendrocytes are essential for the production of myelin, disturbed myelination might be caused by dysfunctional oligodendrocytes or a reduced number of oligodendroglial cells
The aim of the study was to reveal the effect of age on numerical density of oligodendrocytes in the prefrontal cortex in two brain collections—Stanley Foundation Neuropathology Consortium (SFNC) and Mental Health Research Center (MHRC) collections to learn more about the origin of previously found deficit of oligodendroglial cells in the prefrontal cortex in major psychiatric disorders

Summary

Introduction

Disconnection among different brain regions is believed to contribute to the abnormal functioning of neural networks and has been postulated to be central to the pathophysiology of schizophrenia [1,2,3]. The neurobiological substrate of these connectivity abnormalities remains unknown, but recent evidence suggests that abnormalities in myelination and altered oligodendrocyte number and function may be prominent contributors to schizophrenia. Indirect evidence for disturbed structural connectivity in schizophrenia has been obtained from functional neuroimaging and electrophysiologic studies. With growing evidence of disturbed connectivity in schizophrenia, myelin pathology has been a target of recent postmortem studies. Evidence for the involvement of oligodendrocytes and myelin in the pathophysiology of schizophrenia has come from analysis of postmortem tissue subjects with schizophrenia using protein [4, 5] and gene expression studies [5,6,7,8,9,10,11], light, and electron microscopic studies [12,13,14], and in vivo neuroimaging studies [15,16,17,18,19]

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