Oxidative stress, prefrontal cortex hypomyelination and cognitive symptoms in schizophrenia

Schizophrenia (SZ) is a neurodevelopmental disorder with a broad symptomatology, including cognitive symptoms that are thought to arise from the prefrontal cortex (PFC). The neurobiological aetiology of these symptoms remains elusive, yet both impaired redox control and PFC dysconnectivity have been recently implicated. PFC dysconnectivity has been linked to white matter, oligodendrocyte (OL) and myelin abnormalities in SZ patients. Myelin is produced by mature OLs, and OL precursor cells (OPCs) are exceptionally susceptible to oxidative stress. Here we propose a hypothesis for the aetiology of cognitive symptomatology in SZ: the redox-induced prefrontal OPC-dysfunctioning hypothesis. We pose that the combination of genetic and environmental factors causes oxidative stress marked by a build-up of reactive oxygen species that, during late adolescence, impair OPC signal transduction processes that are necessary for OPC proliferation and differentiation, and involve AMP-activated protein kinase, Akt-mTOR-P70S6K and peroxisome proliferator receptor alpha signalling. OPC dysfunctioning coincides with the relatively late onset of PFC myelination, causing hypomyelination and disruption of connectivity in this brain area. The resulting cognitive deficits arise in parallel with SZ onset. Hence, our hypothesis provides a novel neurobiological framework for the aetiology of SZ cognitive symptoms. Future research addressing our hypothesis could have important implications for the development of new (combined) antioxidant- and promyelination-based strategies to treat the cognitive symptoms in SZ.


Nice to hear about cognitive things.thanks for sharing…!!!

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andrey. two things. first, i once learned that too much protein is bad for us with sz. also sugar is a no no especially for us.

just a little bit related but not so much, sorry. judy

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Are there any ideas about how to increase mylenation?

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A number of studies have identified several agents which helped remyelinate cuprizone-treated mice:

It would be interesting to translate these finding into clinical trials… Almost two years ago I mailed a few people who may have an interest in this direction, but didn’t get an answer.

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That’s good that they’re looking at it. The papers are only a few years old, so perhaps there will be progress still. Delayed mylenation apparently is an issue for some children with developmental delays, a different research area but the findings might apply. Children with GDD do have a higher risk of developing schizophrenia.