Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, 250012, China.
Transl Psychiatry. 2023 Jun 15;13(1):206. doi: 10.1038/s41398-023-02496-1.
The dentate gyrus (DG) of the hippocampus encodes contextual information associated with fear, and cell activity in the DG is required for acquisition and extinction of contextual fear. However, the underlying molecular mechanisms are not fully understood. Here we show that mice deficient for peroxisome proliferator-activated receptor-α (PPARα) exhibited a slower rate of contextual fear extinction. Furthermore, selective deletion of PPARα in the DG attenuated, while activation of PPARα in the DG by local infusion of aspirin facilitated extinction of contextual fear. The intrinsic excitability of DG granule neurons was reduced by PPARα deficiency but increased by activation of PPARα with aspirin. Using RNA-Seq transcriptome we found that the transcription level of neuropeptide S receptor 1 (Npsr1) was tightly correlated with PPARα activation. Our results provide evidence that PPARα plays an important role in regulating DG neuronal excitability and contextual fear extinction.
海马齿状回（DG）编码与恐惧相关的上下文信息，DG 中的细胞活动是获得和消除情境恐惧所必需的。然而，其潜在的分子机制尚不完全清楚。在这里，我们发现过氧化物酶体增殖物激活受体-α（PPARα）缺乏的小鼠表现出较慢的情境恐惧消退速度。此外，DG 中选择性敲除 PPARα 会减弱，而局部输注阿司匹林激活 DG 中的 PPARα 则会促进情境恐惧的消退。DG 颗粒神经元的内在兴奋性被 PPARα 缺乏所降低，但被阿司匹林激活 PPARα 所增加。通过 RNA-Seq 转录组分析，我们发现神经肽 S 受体 1（Npsr1）的转录水平与 PPARα 的激活密切相关。我们的研究结果提供了证据，表明 PPARα 在调节 DG 神经元兴奋性和情境恐惧消退中发挥重要作用。
