Abstract

Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.

Dysfunction of GABAergic neurons in the prefrontal cortex has been reported in schizophrenia. Here, the authors use the apomorphine-susceptible rat, which displays some schizophrenia-like behaviors, and show that interneurons in the medial prefrontal cortex are hypomyelinated, which may contribute to this behavioral phenotype.

Details

Title
Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia
Author
Maas, Dorien A 1   VIAFID ORCID Logo  ; Eijsink, Vivian D 2 ; Spoelder Marcia 3 ; van Hulten Josephus A 2 ; De Weerd Peter 4 ; Homberg, Judith R 3 ; Vallès Astrid 5 ; Nait-Oumesmar Brahim 6   VIAFID ORCID Logo  ; Martens Gerard J M 2 

1  Radboud University, Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Nijmegen, The Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605); Sorbonne Université, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris Brain Institute, ICM, Inserm U1127, Paris, France (GRID:grid.5590.9); Radboud University Medical Center, Department of Cognitive Neuroscience, Donders Centre for Medical Neuroscience, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
2  Radboud University, Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Nijmegen, The Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605) 
3  Radboud University Medical Center, Department of Cognitive Neuroscience, Donders Centre for Medical Neuroscience, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
4  Maastricht University, Department of Neurocognition, Faculty of Psychology and Neurosciences, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht University, Maastricht Centre of Systems Biology (MaCSBio), Faculty of Science and Engineering, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
5  Radboud University, Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Nijmegen, The Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605); Maastricht University, Department of Neurocognition, Faculty of Psychology and Neurosciences, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
6  Sorbonne Université, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris Brain Institute, ICM, Inserm U1127, Paris, France (GRID:grid.5012.6) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-16218-4
ProQuest document ID
2401044594
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.