γ-aminobutyric acid (GABA) inhibitory interneurons play a key role in efferent and afferent control of principle neuron activity in the prefrontal cortex (PFC), thereby regulating signal integrity of cognitive and behavioral processes. Recent evidence suggests that specific subtypes of interneurons in the PFC mediate stress-induced depressive-like behaviors. Abnormalities of GABA interneurons, particularly the somatostatin (human, SST; mouse, Sst) subtype, have been reported in postmortem brains of depressed subjects and include sex differences that could explain the increased incidence of depression in women. Here, we analyze the transcriptional profiles and the effects of chronic stress in males vs. females on GABA interneuron subtypes in the PFC. Using Sst- and Parvalbumin-fluorescence tagged reporter mice and fluorescence-activated cell sorting (FACS) combined with RNA sequencing, we identify distinct transcriptome profiles for these interneuron subtypes in the medial PFC. Based on evidence that SST interneurons are altered in depression, we then determined the effects of chronic stress on this interneuron subtype. Chronic stress causes significant dysregulation of several key pathways, including sex-specific differences in the Sst interneuron profiles. The transcriptional pathways altered by chronic stress in males overlap with enriched pathways in non-stressed females. These changes occurred predominantly in decreased expression of elongation initiation factor 2 (EIF2) signaling, suggesting that dysfunction of the translational machinery of SST interneurons could be critical to the development of depressive-like behaviors in males. In addition, SST interneurons from females exposed to chronic stress show dysregulation of different, growth factor signaling pathways.

中文翻译：

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前额叶皮层interneurons显示动态性别特定压力诱导转录组。

γ-氨基丁酸（GABA）抑制性中间神经元在前额叶皮层（PFC）的主要神经元活动的传出和传出控制中起关键作用，从而调节认知和行为过程的信号完整性。最近的证据表明，PFC中特定的中间神经元亚型介导应激诱导的抑郁样行为。据报道，在抑郁症患者的尸检大脑中，GABA interneurons异常，特别是生长抑素（人生长抑素；小鼠，Sst）亚型异常，其中包括性别差异，这可以解释女性抑郁症发病率的增加。在这里，我们分析了男性和女性在PFC中的GABA interneuron亚型的转录特征和慢性应激的影响。使用Sst和Parvalbumin荧光标记的报告基因小鼠和荧光激活的细胞分选（FACS）与RNA测序相结合，我们确定内侧PFC中这些中间神经元亚型的独特转录组概况。基于SST中间神经元在抑郁症中发生改变的证据，然后我们确定了慢性应激对该中间神经元亚型的影响。慢性应激会导致一些关键途径的严重失调，包括Sst中神经元图谱中的性别特异性差异。男性慢性应激改变的转录途径与非应激女性丰富的途径重叠。这些变化主要发生在延伸起始因子2（EIF2）信号表达的降低中，提示SST中神经元翻译机制的功能异常可能对男性抑郁样行为的发展至关重要。此外，来自暴露于慢性应激的雌性的SST interneurons显示出不同的生长因子信号通路的失调。