IMPAIRED mPFC-DEPENDENT SPATIAL WORKING MEMORY IN THE APO-SUS RAT MODEL FOR SCHIZOPHRENIA

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2018-01-30
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en
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Abstract
The neurobiology underlying cognitive symptomatology in schizophrenia (SZ) remains poorly understood and untreated. Prefrontal (PFC) dysconnectivity and both a redox imbalance and oligodendrocyte (OL) dysfunction are thought to be involved in SZ. To study the cognitive symptoms, we used the APO-SUS rat model for SZ. At the behavioral level of the symptoms we focused on the medial PFC (mPFC) and working memory (WM). We report a dysfunctional/immature mPFC in the APO-SUS rats as was evident from the deficits observed in the social interaction test and spatial working memory deficits that were repeatedly shown in three different mPFC-dependent tasks: the continuous delayed alternation, repeated reversal learning and spatial win-shifting. At the molecular level and various ages (PND21, PND90, PND365) APO-SUS rats had altered mRNA expression levels of redox-related genes in the cingulate cortex (Cg), the hippocampus (HPC) and barrel cortex (BC), indicating a general redox impairment. Finally, we report that APO-SUS rats do not differ from APO-UNSUS rats in the mRNA expression levels of myelin- or OL-related genes in Cg, HPC and BC, which together with previous studies from our group indicates an mPFC-specific myelin and OL deficit. We conclude that APO-SUS rats have a redox imbalance that is not mPFC specific but rather spread throughout the brain and a spatial working memory deficit that is mPFC dependent.
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Faculteit der Sociale Wetenschappen