Sex-Specific Transcriptomic Signatures in Brain Regions Critical for Neuropathic Pain-Induced Depression.
Sex-Specific Transcriptomic Signatures in Brain Regions Critical for Neuropathic Pain-Induced Depression.
复制标题
大脑区域中性别特异性转录组特征对神经性疼痛引起的抑郁症至关重要
DOI：
10.3389/fnmol.2022.886916
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
Ye, Xiaojing
中科院分区：
文献类型：
--
作者：
Dai, Weiping;Huang, Shuying;Luo, Yuan;Cheng, Xin;Xia, Pei;Yang, Mengqian;Zhao, Panwu;Zhang, Yingying;Lin, Wei-Jye;Ye, Xiaojing
关键词：
神经性疼痛是一种慢性衰弱性疾病，与抑郁症有很高的共病率。临床报告和动物研究表明，内侧前额叶皮层（mPFC）和前扣带皮层（ACC）在调节神经病理性疼痛的情感症状中起着至关重要的作用。神经病理性疼痛在这两个区域诱导不同的长期结构、功能和生化变化，这些变化被认为是由多波基因转录调控的。然而，这些区域之间的神经性疼痛改变的转录谱的差异在很大程度上是未知的。此外，妇女比男子更容易受到疼痛和抑郁的影响。这种两性异形的分子机制仍有待探索。在这里，我们进行了RNA测序，并分析了雌性和雄性小鼠的mPFC和ACC在备用神经损伤（SNI）后2周的转录谱，这是小鼠开始表现出轻度抑郁症状的早期时间点。我们的研究结果表明，SNI诱导的转录组的变化在很大程度上是不同的雌性和雄性小鼠。有趣的是，雌性小鼠在ACC中表现出比雄性小鼠更强的转录组学变化，而在mPFC中发生了相反的模式。细胞类型富集分析显示，差异表达的基因涉及在神经元，各种类型的胶质细胞和内皮细胞富集的基因。我们进一步进行了基因集富集分析（GSEA），结果显示SNI后女性和男性mPFC中髓鞘发育的显著去富集。在女性ACC中，突触组织的基因集被富集，细胞外基质的基因集在SNI后被去富集，而这样的签名在男性ACC中不存在。总的来说，这些发现揭示了神经性疼痛诱导的转录水平上的区域特异性和性二态性，并为慢性疼痛及其相关的情感障碍提供了新的治疗靶点。
Neuropathic pain is a chronic debilitating condition with a high comorbidity with depression. Clinical reports and animal studies have suggested that both the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) are critically implicated in regulating the affective symptoms of neuropathic pain. Neuropathic pain induces differential long-term structural, functional, and biochemical changes in both regions, which are thought to be regulated by multiple waves of gene transcription. However, the differences in the transcriptomic profiles changed by neuropathic pain between these regions are largely unknown. Furthermore, women are more susceptible to pain and depression than men. The molecular mechanisms underlying this sexual dimorphism remain to be explored. Here, we performed RNA sequencing and analyzed the transcriptomic profiles of the mPFC and ACC of female and male mice at 2 weeks after spared nerve injury (SNI), an early time point when the mice began to show mild depressive symptoms. Our results showed that the SNI-induced transcriptomic changes in female and male mice were largely distinct. Interestingly, the female mice exhibited more robust transcriptomic changes in the ACC than male, whereas the opposite pattern occurred in the mPFC. Cell type enrichment analyses revealed that the differentially expressed genes involved genes enriched in neurons, various types of glia and endothelial cells. We further performed gene set enrichment analysis (GSEA), which revealed significant de-enrichment of myelin sheath development in both female and male mPFC after SNI. In the female ACC, gene sets for synaptic organization were enriched, and gene sets for extracellular matrix were de-enriched after SNI, while such signatures were absent in male ACC. Collectively, these findings revealed region-specific and sexual dimorphism at the transcriptional levels induced by neuropathic pain, and provided novel therapeutic targets for chronic pain and its associated affective disorders.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
神经性疼痛的SNI动物模型中皮肤损伤和未受伤的伤害感受器的基因表达分析。
影响因子：
4.6
作者：
Berta T;Perrin FE;Pertin M;Tonello R;Liu YC;Chamessian A;Kato AC;Ji RR;Decosterd I
通讯作者：
Decosterd I
影响因子：
7.7
作者：
Bonnefil, Valentina;Dietz, Karen;Liu, Jia
通讯作者：
Liu, Jia
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
Synaptotagmin 2是中央抑制突触处的快速Ca（2+）传感器。
影响因子：
8.8
作者：
Chen C;Arai I;Satterfield R;Young SM Jr;Jonas P
通讯作者：
Jonas P