Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats

• DOI: 10.3389/fimmu.2023.1261256
• Publication Date: 2023-11-13T03:46:21Z
• Authors: 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
• Keywords: peripheral infection; Immunology; regional neuroinflammation; Pain; COVID-19; RC581-607; sickness behavior; Rats; 03 medical and health sciences; PET; 0302 clinical medicine; Poly I; Positron-Emission Tomography; Neuroinflammatory Diseases; Animals; fatigue-like symptoms; Immunologic diseases. Allergy

A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context various infections, such as COVID-19. Although pathogenic mechanisms underlying an infection causing fever pain well established, fatigue induced by specific brain regions remain unclear. To elucidate whether how peripheral cause via regional neuroinflammation, we performed a brain-wide investigation neuroinflammation pseudoinfection rat model using [18F]DPA-714 positron emission tomography (PET) imaging analysis, which polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected. Transient lasting for several hours subsequent suppression spontaneous activity few days were poly I:C treatment. Significant increase plasma interleukin (IL)-1β, IL-6 tumour necrosis factor (TNF)-α observed at 2 4 h following PET analysis revealed that uptake significantly increased one day after treatment, dorsal raphe (DR), parvicellular part red nucleus (RPC), A5 A7 noradrenergic nucleus, compared with control group. The accumulation DR, RPC positively correlated fatigue-like behavior, tended to correlate fever. These findings suggest may trigger symptoms fatigue. similar mechanism might be involved