Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study

Natalya A Uranova,Olga V Vikhreva,Diana D Orlovskaya,Valentina I Rachmanova

doi:10.1155/2011/325789

Abstract

Schizophrenia is believed to result from altered neuronal connectivity and impaired myelination. However, there are few direct evidence for myelin abnormalities in schizophrenia. We performed electron microscopic study of myelinated fibers and oligodendrocytes and morphometric study of myelinated fibers in the prefrontal cortex in gray and white matters in schizophrenia and normal controls. Six types of abnormal fibers and ultrastructural alterations of oligodendrocytes were found in schizophrenia. No significant group differences in area density of myelinated fibers were found. Frequency of pathological fibers was increased significantly in gray matter in young and elderly schizophrenia patients and in patients with predominantly positive symptoms. In contrast, in white matter, frequency of altered fibers was increased significantly in elderly patients, in patients with predominantly negative symptoms, and correlated with illness duration. Progressive alterations of myelinated fibers in white matter might be followed by alterations of myelinated fibers in gray matter in schizophrenia.

Highlights

Growing evidence coming from neuroimaging and postmortem studies support the notion that altered neuronal connectivity in schizophrenia is associated with disturbed myelination in different fiber tracts [1,2,3,4,5,6,7,8,9]
Our study addressed the following questions: (1) What kind of ultrastructural abnormalities of myelinated fibers and oligodendrocytes differ schizophrenia subjects from controls, whether an axonal degeneration and loss of myelin occur in schizophrenia? (2) Do the ultrastructural alterations of myelinated fibers in gray matter differ from those in white matter? (3) Are the changes of myelinated fibers associated with age, gender, age at onset, and duration of illness? (4) Is there a link between abnormalities of myelinated fibers and symptoms of schizophrenia and neuroleptic exposure?
Since myelin is produced by oligodendrocytes, these data suggest that the pathology of myelinated nerve fibers in schizophrenia might be due to oligodendrocyte abnormalities

Summary

Introduction

Growing evidence coming from neuroimaging and postmortem studies support the notion that altered neuronal connectivity in schizophrenia is associated with disturbed myelination in different fiber tracts [1,2,3,4,5,6,7,8,9]. Metabolic abnormalities in fronto-striatal-thalamic white matter tracts have been reported in schizophrenia [12]. DTI studies of white matter in schizophrenia demonstrated a significant reduction in fractional anisotropy (FA) in frontal lobe and the relationships between white matter abnormalities and symptoms of the disorder [13,14,15,16]. It is not known whether the abnormalities observed to date reflect a decrease in number of axons, decreased axonal diameter, thinner myelin sheaths, or less coherent fibers

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