Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats.
Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats.
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内侧前额叶皮质中的性别特异性转录特征是大鼠对压力的性别二态性行为反应的基础。
DOI：
10.1503/jpn.220147
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发表时间：
2023-01
影响因子：
4.3
通讯作者：
Wang, Zhen
中科院分区：
文献类型：
--
作者：
Zhang, Ying-Dan;Shi, Dong-Dong;Zhang, Sen;Wang, Zhen
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然未知。我们分别采用不可预测的母体分离（UMS）和成年束缚应激（RS）范式来模拟大鼠在生命早期或成年期的应激。注意到前额叶皮层的性别二型性，我们进行了RNA测序（RNA-Seq），以确定负责对压力的性别二型反应的特定基因或途径。然后，我们进行定量逆转录聚合酶链反应（qRT-PCR），以验证RNA-Seq的结果。暴露于UMS或RS的雌性大鼠对焦虑样行为没有负面影响，而在应激雄性大鼠中PFC的情感功能明显受损。利用差异表达基因（DEG）分析，我们确定了与压力相关的性别特异性转录谱。UMS和RS转录数据集之间存在许多重叠的DEG，其中1406个DEG与生物性别和胁迫相关，而只有117个DEG与胁迫相关。值得注意的是，Uba 52和Rpl 34-psl分别是1406和117个DEG中排名第一的枢纽基因，并且Uba 52高于Rpl 34-psl，表明应激可能对1406个DEG的集合产生更显著的影响。途径分析表明，1406个DEG主要富集在核糖体途径。这些结果通过qRT-PCR证实。在这项研究中确定了与压力相关的性别特异性转录谱，但需要更深入的实验，如单细胞测序和体内雄性和雌性基因网络的操作，以验证我们的发现。我们的研究结果表明，性别特异性的行为反应的压力，并强调在转录水平上的性二态性，揭示了发展性别特异性的治疗策略，压力相关的精神疾病。
Converging evidence suggests that stress alters behavioural responses in a sex-specific manner; however, the underlying molecular mechanisms of stress remain largely unknown. 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. 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, Uba52 and Rpl34-ps1 were the first-ranked hub gene in 1406 and 117 DEGs respectively, and Uba52 was higher than Rp134-ps1, 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. 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. 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.
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影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
10.6
作者：
Parel ST;Peña CJ
通讯作者：
Peña CJ
影响因子：
3.5
作者：
Bianchi, Marzia;Giacomini, Elisa;Magnani, Mauro
通讯作者：
Magnani, Mauro
DOI：
10.1007/s44192-022-00009-y
发表时间：
2022-03-03
期刊：
Discover mental health
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Kobayashi M;Oshima S;Maeyashiki C;Nibe Y;Otsubo K;Matsuzawa Y;Nemoto Y;Nagaishi T;Okamoto R;Tsuchiya K;Nakamura T;Watanabe M
通讯作者：
Watanabe M