@article{846df7e95dc04e64970be9342b868177,
title = "Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia",
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.",
keywords = "MEDIAL PREFRONTAL CORTEX, WORKING-MEMORY DEFICITS, CARD SORTING TEST, ULTRA-HIGH-RISK, PARVALBUMIN INTERNEURONS, ENRICHED ENVIRONMENT, ANIMAL-MODELS, WHITE-MATTER, IN-VIVO, MYELINATION",
author = "Maas, {Dorien A.} and Eijsink, {Vivian D} and Marcia Spoelder and {van Hulten}, {Josephus A} and {De Weerd}, Peter and Homberg, {Judith R.} and Astrid Vall{\`e}s and Brahim Nait-Oumesmar and Martens, {Gerard J.M.}",
note = "Funding Information: The authors wish to thank Dr. Dominique Langui (ICM Quant) for excellent advice and technical assistance concerning electron microscopy, Nick van Bakel, Lydia Pavlidi, Wiebke Schwark, Mary Vlassopulou, Noor van Vugt, Alex van der Starre, and Cyrille Deboux for technical lab assistance. Microscopic imaging of OLIG2-NG2 immunohistochemical staining was performed at the Microscopic Imaging Centre (MIC; Radboud Institute for Molecular Life Sciences, RIMLS, Radboud University Medical Centre, Nijmegen, The Netherlands). All other microscopic imaging was performed at the Paris Brain Institute (ICM) Imaging Facility (ICM Quant, Paris, France), which we thank for their advice and technical assistance concerning electron microscopy, fluorescence imaging, and quantitative analysis, and the ICM Histology Facility (Histomics) for their technical support. This study was supported by grants from the programs {\textquoteleft}Top Talent{\textquoteright} Donders Centre for Medical Neuroscience (to D.A.M.), Investissements d{\textquoteright}Avenir ANR-10-IAIHU-06 (IHU-A-ICM) and ANR-11-INBS-0011 (NeurATRIS) (to B.N.-O.), Van Gogh travel grant (to D.A.M., B.N.-O., and G.J.M.M.), and Dutch Top Institute Pharma grant T5-209 (to V.D.E. and G.J.M.M.). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = may,
day = "11",
doi = "10.1038/s41467-020-16218-4",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}