RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis
Abstract Background Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammatio...
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-021-02356-z |
| _version_ | 1819102676804173824 |
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| author | Yuming Wu Yujing Zhang Bing Xie Amro Abdelgawad Xiaoyan Chen Mengqi Han You Shang Shiying Yuan Jiancheng Zhang |
| author_facet | Yuming Wu Yujing Zhang Bing Xie Amro Abdelgawad Xiaoyan Chen Mengqi Han You Shang Shiying Yuan Jiancheng Zhang |
| author_sort | Yuming Wu |
| collection | DOAJ |
| description | Abstract Background Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment. Methods LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment. Results LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment. Conclusions Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis. |
| first_indexed | 2024-12-22T01:38:21Z |
| format | Article |
| id | doaj.art-9510d9ece79646648c0174fce2e58b2b |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T01:38:21Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-9510d9ece79646648c0174fce2e58b2b2022-12-21T18:43:18ZengBMCJournal of Neuroinflammation1742-20942021-12-0118111310.1186/s12974-021-02356-zRhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axisYuming Wu0Yujing Zhang1Bing Xie2Amro Abdelgawad3Xiaoyan Chen4Mengqi Han5You Shang6Shiying Yuan7Jiancheng Zhang8Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyMidyorks NHS TrustDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment. Methods LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment. Results LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment. Conclusions Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis.https://doi.org/10.1186/s12974-021-02356-zCognitionGut microbiotaLPSNeuroinflammationSubdiaphragmatic vagus nerve |
| spellingShingle | Yuming Wu Yujing Zhang Bing Xie Amro Abdelgawad Xiaoyan Chen Mengqi Han You Shang Shiying Yuan Jiancheng Zhang RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis Journal of Neuroinflammation Cognition Gut microbiota LPS Neuroinflammation Subdiaphragmatic vagus nerve |
| title | RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis |
| title_full | RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis |
| title_fullStr | RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis |
| title_full_unstemmed | RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis |
| title_short | RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis |
| title_sort | rhanp attenuates endotoxin derived cognitive dysfunction through subdiaphragmatic vagus nerve mediated gut microbiota brain axis |
| topic | Cognition Gut microbiota LPS Neuroinflammation Subdiaphragmatic vagus nerve |
| url | https://doi.org/10.1186/s12974-021-02356-z |
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