Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Radboud University, Geert Grooteplein Zuid 26-28, 6525 GA, Nijmegen, The Netherlands.
Paris Brain Institute, ICM, Inserm U1127, Sorbonne Université, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris, France.
Nat Commun. 2020 May 11;11(1):2329. doi: 10.1038/s41467-020-16218-4.
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.
认知功能障碍是精神分裂症的核心特征，据推测是由于青少年前额叶皮层 (PFC) 发育过程中的髓鞘形成以及中间神经元缺陷所致。在这里，我们报告了在具有精神分裂症样特征的阿朴吗啡易感 (APO-SUS) 大鼠模型中，特定的副甲状腺素中间神经元发生了髓鞘缺陷。成年大鼠表现出内侧前额叶皮层 (mPFC) 依赖的认知灵活性障碍，以及 mPFC 中成熟少突胶质细胞和髓鞘化副甲状腺素抑制轴突数量减少。在发育中的 mPFC 中，我们观察到与髓鞘形成相关的基因表达减少，这种情况一直持续到成年期。青少年时期进行的环境丰富处理恢复了副甲状腺素中间神经元的髓鞘减少以及认知灵活性障碍。总之，这些发现强调了副甲状腺素中间神经元髓鞘形成的损伤与精神分裂症相关的认知缺陷有关。
