Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex
Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with d...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661823000737 |
| _version_ | 1797740547048210432 |
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| author | Yong He Yue Wang Heming Yu Yu Tian Xiangyu Chen Chong Chen Yikun Ren Zhi Chen Yi Ren Xue Gong Ke Cheng Xiaolei Liu Lianmei Zhong Yi Guo Peng Xie |
| author_facet | Yong He Yue Wang Heming Yu Yu Tian Xiangyu Chen Chong Chen Yikun Ren Zhi Chen Yi Ren Xue Gong Ke Cheng Xiaolei Liu Lianmei Zhong Yi Guo Peng Xie |
| author_sort | Yong He |
| collection | DOAJ |
| description | Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation. |
| first_indexed | 2024-03-12T14:13:58Z |
| format | Article |
| id | doaj.art-c57628bcb9854c7abc20c23655cd3b7f |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-12T14:13:58Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
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| series | Pharmacological Research |
| spelling | doaj.art-c57628bcb9854c7abc20c23655cd3b7f2023-08-21T04:19:50ZengElsevierPharmacological Research1096-11862023-05-01191106717Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortexYong He0Yue Wang1Heming Yu2Yu Tian3Xiangyu Chen4Chong Chen5Yikun Ren6Zhi Chen7Yi Ren8Xue Gong9Ke Cheng10Xiaolei Liu11Lianmei Zhong12Yi Guo13Peng Xie14NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaNeurology Department of the First affiliated hospital of Kunming Medical University, Kunming, ChinaNeurology Department of the First affiliated hospital of Kunming Medical University, Kunming, China; Correspondence to: NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.Department of Neurology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518020 Guangdong, China; Correspondence to: NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Correspondence to: NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation.http://www.sciencedirect.com/science/article/pii/S1043661823000737NeuroinflammationDepressionAnterior cingulate cortexNr4a2LPS |
| spellingShingle | Yong He Yue Wang Heming Yu Yu Tian Xiangyu Chen Chong Chen Yikun Ren Zhi Chen Yi Ren Xue Gong Ke Cheng Xiaolei Liu Lianmei Zhong Yi Guo Peng Xie Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex Pharmacological Research Neuroinflammation Depression Anterior cingulate cortex Nr4a2 LPS |
| title | Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex |
| title_full | Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex |
| title_fullStr | Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex |
| title_full_unstemmed | Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex |
| title_short | Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex |
| title_sort | protective effect of nr4a2 nurr1 against lps induced depressive like behaviors via regulating activity of microglia and camkii neurons in anterior cingulate cortex |
| topic | Neuroinflammation Depression Anterior cingulate cortex Nr4a2 LPS |
| url | http://www.sciencedirect.com/science/article/pii/S1043661823000737 |
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