Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02503-0 |
| _version_ | 1828333808441622528 |
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| author | Yu-Ting Zhao Jie Deng He-Ming Liu Jia-You Wei Hai-Ting Fan Meng Liu Ting Xu Ting-Feng Chen Jing-Yi He Wei-Ming Sun Tao-Yu Jia Xue-Qin Zhang Wen-Jun Xin |
| author_facet | Yu-Ting Zhao Jie Deng He-Ming Liu Jia-You Wei Hai-Ting Fan Meng Liu Ting Xu Ting-Feng Chen Jing-Yi He Wei-Ming Sun Tao-Yu Jia Xue-Qin Zhang Wen-Jun Xin |
| author_sort | Yu-Ting Zhao |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-13T21:24:52Z |
| format | Article |
| id | doaj.art-34d46d57104642c09ed5d2d79cca73ba |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T21:24:52Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-34d46d57104642c09ed5d2d79cca73ba2022-12-22T02:29:21ZengBMCJournal of Neuroinflammation1742-20942022-06-0119111610.1186/s12974-022-02503-0Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in ratsYu-Ting Zhao0Jie Deng1He-Ming Liu2Jia-You Wei3Hai-Ting Fan4Meng Liu5Ting Xu6Ting-Feng Chen7Jing-Yi He8Wei-Ming Sun9Tao-Yu Jia10Xue-Qin Zhang11Wen-Jun Xin12Neuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityGuangzhou First People’s HospitalNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityGuangzhou First People’s HospitalGuangzhou First People’s HospitalNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Applied Psychology, The Affiliated Brain Hospital of Guangzhou Medical UniversityNeuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12974-022-02503-0ComorbidDepressionNeuropathic painSpared nerve injuryPrelimbic cortexIL-6 |
| spellingShingle | Yu-Ting Zhao Jie Deng He-Ming Liu Jia-You Wei Hai-Ting Fan Meng Liu Ting Xu Ting-Feng Chen Jing-Yi He Wei-Ming Sun Tao-Yu Jia Xue-Qin Zhang Wen-Jun Xin Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats Journal of Neuroinflammation Comorbid Depression Neuropathic pain Spared nerve injury Prelimbic cortex IL-6 |
| title | Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| title_full | Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| title_fullStr | Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| title_full_unstemmed | Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| title_short | Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| title_sort | adaptation of prelimbic cortex mediated by il 6 stat3 acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats |
| topic | Comorbid Depression Neuropathic pain Spared nerve injury Prelimbic cortex IL-6 |
| url | https://doi.org/10.1186/s12974-022-02503-0 |
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