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Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia

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  • Dorien A. Maas

    (Radboud University
    Sorbonne Université, CNRS UMR 7225, Hôpital Pitié-Salpêtrière
    Radboud University Medical Center)

  • Vivian D. Eijsink

    (Radboud University)

  • Marcia Spoelder

    (Radboud University Medical Center)

  • Josephus A. Hulten

    (Radboud University)

  • Peter Weerd

    (Maastricht University
    Maastricht University)

  • Judith R. Homberg

    (Radboud University Medical Center)

  • Astrid Vallès

    (Radboud University
    Maastricht University)

  • Brahim Nait-Oumesmar

    (Sorbonne Université, CNRS UMR 7225, Hôpital Pitié-Salpêtrière)

  • Gerard J. M. Martens

    (Radboud University)

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.

Suggested Citation

  • Dorien A. Maas & Vivian D. Eijsink & Marcia Spoelder & Josephus A. Hulten & Peter Weerd & Judith R. Homberg & Astrid Vallès & Brahim Nait-Oumesmar & Gerard J. M. Martens, 2020. "Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16218-4
    DOI: 10.1038/s41467-020-16218-4
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    Cited by:

    1. Li-Pao Fang & Na Zhao & Laura C. Caudal & Hsin-Fang Chang & Renping Zhao & Ching-Hsin Lin & Nadine Hainz & Carola Meier & Bernhard Bettler & Wenhui Huang & Anja Scheller & Frank Kirchhoff & Xianshu Ba, 2022. "Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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