Characterization of age-related myelination deficits in a rat model for schizophrenia

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Issue Date
2016-07-01
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en
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Abstract
Schizophrenia (SZ) is a debilitating neuropsychiatric disorder that affects millions of people around the world. A growing body of evidence points towards the involvement of hypomyelination of the prefrontal cortex (PFC) in the development of the cognitive symptoms of the disorder. Our hypothesis is that SZ patients exhibit elevated oxidative stress (i.e. redox imbalance) throughout the brain early in development and this disrupts the ongoing process of myelination in the late-maturing PFC, resulting in clinical manifestations of cognitive dysfunction. To tackle the neurophysiological underpinnings and postnatal developmental timing of such a mechanism, we combined molecular and cellular analysis in the apomorphine-susceptible (APO-SUS) rat model for schizophrenia, using APO-UNSUS rats as their control counterparts. First, we assessed the mRNA expression levels of genes related to myelin, oxidative stress and oligodendrocytes (OLs, the myelinating glia of the central nervous system) in the mPFC, striatum and corpus callosum of post-natal day (PND) 21 and PND28 male animals. Secondly, we used immunohistochemistry to assess differences in the percentage of OLs and their precursors in the mPFC, striatum, corpus callosum and hippocampus of PND21 and PND90 male rats, as well as the extent of myelination in axons of the mPFC and barrel cortex of these animals. The results showed that, while differential expression in redox-related genes is already present at PND21 in multiple brain regions, myelin- and OL-related molecular and cellular abnormalities are more prominent in animals aged PND28 and older, and occur specifically in the APO-SUS mPFC. The results of this study provide more insights into the neuropathology of SZ and clues for developing therapeutic approaches for the disorder.
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Faculteit der Sociale Wetenschappen