PMID- 34261577 OWN - NLM STAT- MEDLINE DCOM- 20220511 LR - 20220511 IS - 1001-9294 (Print) IS - 1001-9294 (Linking) VI - 37 IP - 1 DP - 2022 Mar 31 TI - Minocycline Activates the Nucleus of the Solitary Tract-Associated Network to Alleviate Lipopolysaccharide-Induced Neuroinflammation. PG - 1-14 LID - 10.24920/003954 [doi] AB - Objective To examine the neuroanatomical substrates underlying the effects of minocycline in alleviating lipopolysaccharide (LPS)-induced neuroinflammation. Methods Forty C57BL/6 male mice were randomly and equally divided into eight groups. Over three conse-cutive days, saline was administered to four groups of mice and minocycline to the other four groups. Immediately after the administration of saline or minocycline on the third day, two groups of mice were additionally injected with saline and the other two groups were injected with LPS. Six or 24 hours after the last injection, mice were sacrificed and the brains were removed. Immunohistochemical staining across the whole brain was performed to detect microglia activation via Iba1 and neuronal activation via c-Fos. Morphology of microglia and the number of c-Fo-positive neurons were analyzed by Image-Pro Premier 3D. One-way ANOVA and Fisher's least-significant differences were employed for statistical analyses. Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by reduced activation of microglia in multiple brain regions, including the shell part of the nucleus accumbens (Acbs), paraventricular nucleus (PVN) of the hypothalamus, central nucleus of the amygdala (CeA), locus coeruleus (LC), and nucleus tractus solitarius (NTS). Minocycline significantly increased the number of c-Fo-positive neurons in NTS and area postrema (AP) after LPS treatment. Furthermore, in NTS-associated brain areas, including LC, lateral parabrachial nucleus (LPB), periaqueductal gray (PAG), dorsal raphe nucleus (DR), amygdala, PVN, and bed nucleus of the stria terminali (BNST), minocycline also significantly increased the number of c-Fo-positive neurons after LPS administration. Conclusion Minocycline alleviates LPS-induced neuroinflammation in multiple brain regions, possibly due to increased activation of neurons in the NTS-associated network. FAU - Xiu, Jian-Bo AU - Xiu JB AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. AD - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China. FAU - Li, Lan-Lan AU - Li LL AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. AD - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China. FAU - Xu, Qi AU - Xu Q AD - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. AD - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China. LA - eng GR - 81625008, 81930104, and 31970952/National Natural Science Foundation of China/ GR - 2016YFC1306700/the National Key Research and Development Program of China/ PT - Journal Article PL - China TA - Chin Med Sci J JT - Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih JID - 9112559 RN - 0 (Lipopolysaccharides) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Female MH - *Lipopolysaccharides/toxicity MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Minocycline/pharmacology MH - Neuroinflammatory Diseases MH - Solitary Nucleus OTO - NOTNLM OT - depression OT - lipopolysaccharide OT - microglia OT - neuroinflammation OT - nucleus tractus solitaries EDAT- 2021/07/16 06:00 MHDA- 2022/05/12 06:00 CRDT- 2021/07/15 05:35 PHST- 2021/07/16 06:00 [pubmed] PHST- 2022/05/12 06:00 [medline] PHST- 2021/07/15 05:35 [entrez] AID - 3954 [pii] AID - 10.24920/003954 [doi] PST - ppublish SO - Chin Med Sci J. 2022 Mar 31;37(1):1-14. doi: 10.24920/003954.