Hypomyelination of interneurons in the APO-SUS rat model for schizophrenia

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2019-07-01

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en

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Schizophrenia is a neurodevelopmental disorder that affects about 0,5% of the world population. Symptoms can be categorized into positive, negative, and cognitive clusters. Although most research and treatment currently is focused on the positive symptoms (such as hallucinations), cognitive symptoms represent another core feature of the disorder. The current study investigates the neurobiological mechanism underlying cognitive symptoms of schizophrenia by using the APO-SUS rat model for schizophrenia. Using electron microscopy, we found that the prefrontal cortex (PFC) of APO-SUS rats contains fewer myelinated axons than the PFC of APO-UNSUS rats. This effect is normalized by environmental enrichment of the home cages of the APO-SUS rats. Additionally, using immunofluorescence on 70 nm ultrathin slices of PFC, we were able to visualise individual myelin sheaths and intra-axonal GABA, allowing us to quantify the density of myelinated interneurons. We found that in APO-SUS PFC a lower percentage of myelinated axons was GABAergic than in APO-UNSUS PFC. Together, these data show that in the APO-SUS rat model for schizophrenia interneurons are subject to hypomyelination, and that this defect can be rescued by environmental enrichment.

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Faculteit der Sociale Wetenschappen