Minocycline Activates the Nucleus of the Solitary Tract-Associated Network to Alleviate Lipopolysaccharide-Induced Neuroinflammation
米诺环素激活孤束相关网络核以减轻脂多糖诱导的神经炎症
ミノサイクリンは孤束関連ネットワークの核を活性化して、リポ多糖誘発性神経炎症を軽減します
미노사이클린은 지방다당류로 인한 신경염증을 완화하기 위해 고립로 관련 네트워크의 핵을 활성화합니다
La minociclina activa el núcleo de la red asociada al tracto solitario para aliviar la neuroinflamación inducida por lipopolisacáridos
La minocycline active le noyau du réseau associé aux voies solitaires pour soulager la neuroinflammation induite par les lipopolysaccharides
Миноциклин активирует ядро сети, связанной с солитарным трактом, для облегчения индуцированного липополисахаридами нейровоспаления
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
中国 北京 中国医学科学院基础医学研究所 北京协和医学院基础学院 医学分子生物学国家重点实验室
² Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China
中国 北京 中国医学科学院神经科学中心
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.
