Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice
Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice
复制标题
星形胶质细胞中肝脏 X 受体 β 的丢失通过调节小鼠内侧前额叶皮层的突触传递导致焦虑样行为。
DOI：
10.1038/s41380-021-01139-5
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发表时间：
2021-05-07
影响因子：
11
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
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作者：
Li, Xin;Zhong, Hongyu;Fan, Xiaotang
星形胶质细胞是突触传递的组成部分，其功能障碍导致神经精神疾病，如焦虑和抑郁。肝脏X受体β（LXR β）在星形胶质细胞中表达，LXR β全基因敲除小鼠显示突触形成受损。为了确定LXR β在星形胶质细胞中的作用，我们使用条件性Cre-loxP系统从星形胶质细胞中特异性去除LXR β。我们发现，这种缺失导致成年雄性小鼠的焦虑样行为，但不是抑郁样行为。这种行为表型可以通过选择性删除内侧前额叶皮层（mPFC）星形胶质细胞中的LXR β而完全再现。mPFC第V层锥体神经元参与情绪行为。我们发现，有一个增加的自发兴奋性突触传递的V层锥体神经元的mPFC的这些小鼠。尽管树突棘的外观和数量正常，但这与树突复杂性的增加同时发生。此外，RNA测序的基因本体分析显示，星形胶质细胞LXR β的缺失导致mPFC中突触传递过程的丰富。最后，我们还证实，在第V层锥体神经元的兴奋性突触传递重整减轻了小鼠的焦虑与星形胶质细胞LXR β缺失mPFC。总之，我们的研究结果表明，mPFC中的星形胶质细胞LXR β在突触传递的调节中至关重要，这为治疗焦虑样行为提供了一个潜在的新靶点。
Astrocytes are integral components of synaptic transmission, and their dysfunction leads to neuropsychiatric disorders such as anxiety and depression. Liver X receptor beta (LXR beta) is expressed in astrocytes, and LXR beta global knockout mice shows impaired synaptic formation. In order to define the role of LXR beta in astrocytes, we used a conditional Cre-loxP system to specifically remove LXR beta from astrocytes. We found that this deletion caused anxiety-like but not depressive-like behaviors in adult male mice. This behavioral phenotype could be completely reproduced by selective deletion of LXR beta in astrocytes in the medial prefrontal cortex (mPFC). Pyramidal neurons in layer V of mPFC are involved in mood behaviors. We found that there was an increased spontaneous excitatory synaptic transmission in layer V pyramidal neurons of the mPFC of these mice. This was concurrent with increased dendritic complexity, despite normal appearance and number of dendritic spines. In addition, gene ontology analysis of RNA sequencing revealed that deletion of astrocytic LXR beta led to the enrichment of the process of synaptic transmission in mPFC. Finally, we also confirmed that renormalized excitatory synaptic transmission in layer V pyramidal neurons alleviated the anxiety in mice with astrocytic LXR beta deletion in mPFC. Together, our findings reveal that astrocytic LXR beta in mPFC is critical in the regulation of synaptic transmission, and this provides a potential new target for treatment of anxiety-like behavior.