Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats
IntroductionA series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mecha...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261256/full |
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| author | Danxi Li Danxi Li Danxi Li Di Hu Yuta Ochi Wakiko Arakaki Aya Mawatari Mika Shigeta Yuping Wu Emi Hayashinaka Hiroyuki Neyama Tsuyoshi Tahara Yasuhiro Wada Feng Li Hisashi Doi Yasuyoshi Watanabe Yilong Cui |
| author_facet | Danxi Li Danxi Li Danxi Li Di Hu Yuta Ochi Wakiko Arakaki Aya Mawatari Mika Shigeta Yuping Wu Emi Hayashinaka Hiroyuki Neyama Tsuyoshi Tahara Yasuhiro Wada Feng Li Hisashi Doi Yasuyoshi Watanabe Yilong Cui |
| author_sort | Danxi Li |
| collection | DOAJ |
| description | IntroductionA series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear.MethodsTo elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [18F]DPA-714 positron emission tomography (PET) imaging analysis, in which the polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected.ResultsTransient fever lasting for several hours and subsequent suppression of spontaneous activity lasting a few days were induced by poly I:C treatment. Significant increase in plasma interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were observed at 2 and 4 h following poly I:C treatment. PET imaging analysis revealed that the brain uptake of [18F]DPA-714 was significantly increased in several brain regions one day after poly I:C treatment, such as the dorsal raphe (DR), parvicellular part of red nucleus (RPC), A5 and A7 noradrenergic nucleus, compared with the control group. The accumulation of [18F]DPA-714 in the DR, RPC and A5 was positively correlated with subsequent fatigue-like behavior, and that in the A7 tended to positively correlate with fever.DiscussionThese findings suggest that peripheral infection may trigger regional neuroinflammation, which may cause specific symptoms such as fatigue. A similar mechanism might be involved in COVID-19. |
| first_indexed | 2024-03-11T10:58:45Z |
| format | Article |
| id | doaj.art-f92d6feda9974ae5b02cf72767b61400 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T10:58:45Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f92d6feda9974ae5b02cf72767b614002023-11-13T03:46:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12612561261256Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in ratsDanxi Li0Danxi Li1Danxi Li2Di Hu3Yuta Ochi4Wakiko Arakaki5Aya Mawatari6Mika Shigeta7Yuping Wu8Emi Hayashinaka9Hiroyuki Neyama10Tsuyoshi Tahara11Yasuhiro Wada12Feng Li13Hisashi Doi14Yasuyoshi Watanabe15Yilong Cui16Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanDepartment of Chinese Medicine Diagnostics, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaInstitute for Brain Disorders, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Labeling Chemistry, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Labeling Chemistry, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanDepartment of Chinese Medicine Diagnostics, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaLaboratory for Labeling Chemistry, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanIntroductionA series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear.MethodsTo elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [18F]DPA-714 positron emission tomography (PET) imaging analysis, in which the polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected.ResultsTransient fever lasting for several hours and subsequent suppression of spontaneous activity lasting a few days were induced by poly I:C treatment. Significant increase in plasma interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were observed at 2 and 4 h following poly I:C treatment. PET imaging analysis revealed that the brain uptake of [18F]DPA-714 was significantly increased in several brain regions one day after poly I:C treatment, such as the dorsal raphe (DR), parvicellular part of red nucleus (RPC), A5 and A7 noradrenergic nucleus, compared with the control group. The accumulation of [18F]DPA-714 in the DR, RPC and A5 was positively correlated with subsequent fatigue-like behavior, and that in the A7 tended to positively correlate with fever.DiscussionThese findings suggest that peripheral infection may trigger regional neuroinflammation, which may cause specific symptoms such as fatigue. A similar mechanism might be involved in COVID-19.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261256/fullfatigue-like symptomsregional neuroinflammationperipheral infectionPETsickness behavior |
| spellingShingle | Danxi Li Danxi Li Danxi Li Di Hu Yuta Ochi Wakiko Arakaki Aya Mawatari Mika Shigeta Yuping Wu Emi Hayashinaka Hiroyuki Neyama Tsuyoshi Tahara Yasuhiro Wada Feng Li Hisashi Doi Yasuyoshi Watanabe Yilong Cui Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats Frontiers in Immunology fatigue-like symptoms regional neuroinflammation peripheral infection PET sickness behavior |
| title | Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats |
| title_full | Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats |
| title_fullStr | Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats |
| title_full_unstemmed | Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats |
| title_short | Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats |
| title_sort | regional neuroinflammation induced by peripheral infection contributes to fatigue like symptoms a 18f dpa 714 positron emission tomography study in rats |
| topic | fatigue-like symptoms regional neuroinflammation peripheral infection PET sickness behavior |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261256/full |
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