Chinese Medical Sciences Journal

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Minocycline Activates the Nucleus of the Solitary Tract-associated Network to Alleviate Lipopolysaccharide-induced Neuroinflammation

Jianbo Xiu1,2, Lanlan Li1,2, Qi Xu1,2*   

  1. 1 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
    2 Neuroscience center, Chinese Academy of Medical Sciences, Beijing, 100005, China

  • 收稿日期:2021-06-10 接受日期:2021-06-29 出版日期:2021-06-30 发布日期:2021-06-30

Minocycline Activates the Nucleus of the Solitary Tract-associated Network to Alleviate Lipopolysaccharide-induced Neuroinflammation

Jianbo Xiu1,2, Lanlan Li1,2, Qi Xu1,2*   

  1. 1 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
    2 Neuroscience center, Chinese Academy of Medical Sciences, Beijing, 100005, China

  • Received:2021-06-10 Accepted:2021-06-29 Online:2021-06-30 Published:2021-06-30

摘要:


Objective  To examine the neuroanatomical substrates underlying the effects of minocycline on alleviating LPS-induced neuroinflammation.

Methods  Forty C57BL/6 male mice were randomly and equally divided into eight groups. Over three consecutive 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 lipopolysaccharide (LPS). Six or twenty-four hours after the last injection, mice were sacrificed to remove the brains. Immunohistochemistry 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-Fos positive neurons were analyzed by Image-Pro Premier 3D. One-way ANOVA and Fisher’s least-significant differences were employed for statistical analysis.
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 of the hypothalamus (PVN), central nucleus of the amygdala (CeA), locus coeruleus (LC), and nucleus tractus solitarius (NTS). Minocycline significantly increased the number of c-Fos 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-Fos positive neurons after LPS administration.
Conclusion  The present study shows that minocycline alleviates LPS-induced neuroinflammation in multiple brain regions. The effects may result from increased activation of neurons in the NTS-associated network.

关键词: Neuroinflammation, lipopolysaccharide, depression, nucleus tractus solitaries, microglia

Abstract:


Objective  To examine the neuroanatomical substrates underlying the effects of minocycline on alleviating LPS-induced neuroinflammation.

Methods  Forty C57BL/6 male mice were randomly and equally divided into eight groups. Over three consecutive 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 lipopolysaccharide (LPS). Six or twenty-four hours after the last injection, mice were sacrificed to remove the brains. Immunohistochemistry 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-Fos positive neurons were analyzed by Image-Pro Premier 3D. One-way ANOVA and Fisher’s least-significant differences were employed for statistical analysis.
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 of the hypothalamus (PVN), central nucleus of the amygdala (CeA), locus coeruleus (LC), and nucleus tractus solitarius (NTS). Minocycline significantly increased the number of c-Fos 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-Fos positive neurons after LPS administration.
Conclusion  The present study shows that minocycline alleviates LPS-induced neuroinflammation in multiple brain regions. The effects may result from increased activation of neurons in the NTS-associated network.

Key words: Neuroinflammation,  lipopolysaccharide,  depression,  nucleus tractus solitaries,  microglia

基金资助:

National Natural Science Foundation of China (81625008, 81930104, and 31970952), the National Key Research and Development Program of China (2016YFC1306700).

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