内侧前额皮质中性别特异性转录特征，其基础是大鼠对应激的性别二态性行为反应。
Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats.
机构信息
From the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.-D. Zhang, Shi, S. Zhang, Wang); the Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Shi, S. Zhang, Wang); and the Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Wang).
From the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.-D. Zhang, Shi, S. Zhang, Wang); the Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Shi, S. Zhang, Wang); and the Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Wang)
出版信息
J Psychiatry Neurosci. 2023 Feb 16;48(1):E61-E73. doi: 10.1503/jpn.220147. Print 2023 Jan-Feb.
BACKGROUND
Converging evidence suggests that stress alters behavioural responses in a sex-specific manner; however, the underlying molecular mechanisms of stress remain largely unknown.
METHODS
We adapted unpredictable maternal separation (UMS) and adult restraint stress (RS) paradigms to mimic stress in rats in early life or adulthood, respectively. The sexual dimorphism of the prefrontal cortex was noted, and we performed RNA sequencing (RNA-Seq) to identify specific genes or pathways responsible for sexually dimorphic responses to stress. We then performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the results of RNA-Seq.
RESULTS
Female rats exposed to either UMS or RS showed no negative effects on anxiety-like behaviours, whereas the emotional functions of the PFC were impaired markedly in stressed male rats. Leveraging differentially expressed genes (DEG) analyses, we identified sex-specific transcriptional profiles associated with stress. There were many overlapping DEGs between UMS and RS transcriptional data sets, where 1406 DEGs were associated with both biological sex and stress, while only 117 DEGs were related to stress. Notably, and were the first-ranked hub gene in 1406 and 117 DEGs respectively, and was higher than , suggesting that stress may have led to a more pronounced effect on the set of 1406 DEGs. Pathway analysis revealed that 1406 DEGs were primarily enriched in ribosomal pathway. These results were confirmed by qRT-PCR.
LIMITATIONS
Sex-specific transcriptional profiles associated with stress were identified in this study, but more in-depth experiments, such as single-cell sequencing and manipulation of male and female gene networks in vivo, are needed to verify our findings.
CONCLUSION
Our findings show sex-specific behavioural responses to stress and highlight sexual dimorphism at the transcriptional level, shedding light on developing sex-specific therapeutic strategies for stress-related psychiatric disorders.
背景
越来越多的证据表明，压力以性别特异性的方式改变行为反应；然而，压力的潜在分子机制在很大程度上仍是未知的。
方法
我们分别采用不可预测的母体分离（UMS）和成年束缚应激（RS）范式来模拟生命早期或成年期的应激。注意到前额叶皮质的性别二态性，并进行 RNA 测序（RNA-Seq）以鉴定负责应激的性别二态性反应的特定基因或途径。然后，我们进行了定量逆转录聚合酶链反应（qRT-PCR）以验证 RNA-Seq 的结果。
结果
暴露于 UMS 或 RS 的雌性大鼠在焦虑样行为方面没有受到负面影响，而应激雄性大鼠的 PFC 情绪功能明显受损。利用差异表达基因（DEG）分析，我们确定了与应激相关的性别特异性转录谱。UMS 和 RS 转录数据集之间有许多重叠的 DEG，其中 1406 个 DEG 与生物性别和应激都有关，而只有 117 个 DEG 与应激有关。值得注意的是，和分别是 1406 个和 117 个 DEG 中的第一个排名的枢纽基因，并且高于，这表明应激可能对 1406 个 DEG 产生了更显著的影响。通路分析显示，1406 个 DEG 主要富集在核糖体途径中。这些结果通过 qRT-PCR 得到了证实。
局限性
本研究确定了与应激相关的性别特异性转录谱，但需要更多深入的实验，如单细胞测序和体内操纵雄性和雌性基因网络，以验证我们的发现。
结论
我们的研究结果表明，应激存在性别特异性的行为反应，并强调了转录水平的性别二态性，为开发与应激相关的精神障碍的性别特异性治疗策略提供了线索。
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