Institut für Neurophysiologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Charité Platz 1, 10117, Berlin, Germany.
Institut für Biochemie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Charité Platz 1, 10117, Berlin, Germany.
Sci Rep. 2018 Jun 22;8(1):9545. doi: 10.1038/s41598-018-27830-2.
Dysfunction of parvalbumin (PV)-expressing interneurons is thought to underlie the alterations of gamma-band oscillations observed in schizophrenia. Although the pathomechanisms of this disease remain unclear, oxidative stress induced by NMDA receptor (NMDAR) hypofunction and decreased glutathione (GSH) synthesizing capacity have been shown to lead to PV-loss and aberrant oscillatory activity. However, the individual contributions of NMDAR-inhibition and GSH-depletion to the developmental alterations observed in schizophrenia are largely unknown. We therefore investigated each condition in isolation using hippocampal slice cultures wherein interneuron maturation occurs entirely in vitro. Although both treatments caused oxidative stress, NMDAR-inhibition led to an immediate reduction in gamma oscillation frequency and a delayed loss of PV. In contrast, GSH-depletion immediately decreased PV expression and increased power, without affecting frequency. Hence, although disturbances of PV-expression and gamma oscillations coexist in schizophrenia, they can arise from separate pathological processes.
功能失调的钙结合蛋白（PV）表达中间神经元被认为是精神分裂症中观察到的γ波段振荡改变的基础。尽管这种疾病的发病机制仍不清楚，但 NMDA 受体（NMDAR）功能低下引起的氧化应激和谷胱甘肽（GSH）合成能力下降已被证明导致 PV 丢失和异常振荡活性。然而，NMDAR 抑制和 GSH 耗竭对精神分裂症中观察到的发育改变的个体贡献在很大程度上尚不清楚。因此，我们使用完全在体外发生中间神经元成熟的海马切片培养物分别研究每种情况。尽管两种处理都导致了氧化应激，但 NMDAR 抑制导致γ振荡频率立即降低和 PV 延迟丢失。相比之下，GSH 耗竭立即降低 PV 表达并增加功率，而不影响频率。因此，尽管精神分裂症中存在 PV 表达和γ振荡的紊乱，但它们可能来自不同的病理过程。
