Transcriptome Analysis of the Mouse Medial Prefrontal Cortex in a Chronic Constriction Injury Model

Transcriptome Analysis of the Mouse Medial Prefrontal Cortex in a Chronic Constriction Injury Model
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DOI:
10.1007/s12017-023-08742-5
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发表时间:
2023-03-27
影响因子:
3.5
通讯作者:
Cao,Hong
Cao,Hong
中科院分区:
医学3区
文献类型:
--
作者:
Zheng,Qi-Min;Zhou,Zi-Rui;Cao,Hong

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内侧前额叶皮层(mPFC)对疼痛的感觉和情感/认知成分都至关重要。然而,潜在的机制在很大程度上仍然未知。在这里,我们使用RNA测序(RNA-seq)技术检测了慢性疼痛小鼠mPFC中转录组谱的变化。通过坐骨神经慢性收缩损伤(CCI)建立小鼠周围神经性疼痛模型。术后4周,CCI小鼠出现持续的机械异常性疼痛和热痛觉过敏,以及认知障碍。CCI手术后4周进行rna测序。与对照组相比,RNA-seq在CCI模型小鼠同侧和对侧mPFC分别鉴定出309个和222个差异表达基因(deg)。氧化石墨烯分析表明,这些基因的功能主要富集于免疫和炎症相关过程,如干扰素γ的产生和细胞因子的分泌。KEGG分析进一步发现,参与神经活性配体-受体相互作用信号通路和帕金森病通路的基因富集,这些基因已被报道在慢性神经痛和认知功能障碍中起重要作用。我们的研究可能为神经性疼痛和疼痛相关合并症的可能机制提供见解。
The medial prefrontal cortex (mPFC) is critical for both the sensory and emotional/cognitive components of pain. However, the underlying mechanism remains largely unknown. Here, we examined changes in the transcriptomic profiles in the mPFC of mice with chronic pain using RNA sequencing (RNA-seq) technology. A mouse model of peripheral neuropathic pain was established via chronic constriction injury (CCI) of the sciatic nerve. CCI mice developed sustained mechanical allodynia and thermal hyperalgesia, as well as cognitive impairment four weeks after surgery. RNA-seq was conducted 4 weeks after CCI surgery. Compared with contral group, RNA-seq identified a total 309 and 222 differentially expressed genes (DEGs) in the ipsilateral and contralateral mPFC of CCI model mice, respectively. GO analysis indicated that the functions of these genes were mainly enriched in immune- and inflammation-related processes such as interferon-gamma production and cytokine secretion. KEGG analysis further showed the enrichment of genes involved in the neuroactive ligand–receptor interaction signaling pathway and Parkinson disease pathway that have been reported to be importantly involved in chronic neuralgia and cognitive dysfunction. Our study may provide insights into the possible mechanisms underlying neuropathic pain and pain-related comorbidities.