Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.
Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.
复制标题
IL-6/STAT3/Acp5 通路介导的前边缘皮层适应导致大鼠神经病理性疼痛和抑郁的共病
DOI：
10.1186/s12974-022-02503-0
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发表时间：
2022-06-11
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
脑区的适应是神经系统疾病发生和维持的基础。前边缘皮层（PrL）参与痛觉的情感成分。然而，是否以及如何适应的PrL有助于神经病理性疼痛和抑郁症的共病是未知的。本研究采用静息态功能磁共振成像（rs-fMRI）、基因敲除或基因过表达等方法，结合免疫组织化学、电生理和行为学方法，系统研究了PrL区域在神经病理性疼痛/抑郁共病发病机制中的作用。在获得备用神经损伤（SNI）诱导的合并症后，PrL活性和锥体神经元兴奋性降低，PrL神经元抗酒石酸骨钙素酸性磷酸酶5（Acp 5）表达上调。在锥体神经元中Acp 5基因敲低，而不是小清蛋白（PV）神经元或生长抑素（SST）神经元，减轻了共病大鼠的尖峰数量减少，抑郁样行为和机械异常性疼痛。Acp 5在PrL锥体神经元中的过表达减少了未处理大鼠的锋电位数，并诱导了共病样行为。此外，白细胞介素-6（IL-6），磷酸化STAT 3（p-STAT 3）和乙酰化组蛋白H3（Ac-H3）的表达在获得共病后显著增加。STAT 3与Acp 5基因启动子结合的增加以及STAT 3与p300之间的相互作用增强了组蛋白H3的乙酰化，促进了模型啮齿动物PrL中Acp 5的转录。抑制IL-6/STAT 3通路可抑制Acp 5的上调，减轻大鼠的类共病行为。这些数据表明，IL-6/STAT 3/Acp 5途径介导的PrL适应导致了SNI诱导的神经性疼痛/抑郁的共病。
The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.
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DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
5.3
作者：
Li, Jicheng;Li, Yang;Zhao, Hua
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炎症：抑郁症迷在高温下火焰和盛宴。
DOI：
10.1176/appi.ajp.2015.15020152
发表时间：
2015-11-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
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通讯作者：
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影响因子：
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