促炎细胞因子
小胶质细胞
炎症
神经炎症
脂肪因子
血脑屏障
医学
细胞因子
免疫学
海马结构
病态行为
内分泌学
内科学
中枢神经系统
瘦素
肥胖
作者
Lianru Ji,Lang Zhang,Zhi Liu,Sufang Zhong,X.-M. Liu,Zhiping Liu,Wai Sang Poon,Yonggui Song,Baodong Chen,Rikang Wang
标识
DOI:10.1016/j.mce.2023.111990
摘要
Neuro-inflammation and blood-brain barrier (BBB) dysfunction are associated with depression. Evidence shows that adipokines enter the brain from the circulation, which regulates depressive behaviors. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about its role in neuro-inflammation and mood-relevant behavior. Our results showed omentin-1 knockout mice (Omentin-1-/-) increased susceptibility to anxiety and depressive-like behaviors, which are associated with abnormalities of cerebral blood flow (CBF) and impaired BBB permeability. Moreover, omentin-1 depletion significantly increased hippocampal pro-inflammatory cytokines (IL-1β, TNFα, IL-6), caused microglial activation, inhibited hippocampus neurogenesis, and resulted in autophagy impairment by dysregulating ATG genes. Omentin-1 deficiency also sensitized mice to the behavioral changes induced by lipopolysaccharide (LPS), suggesting that omentin-1 could rescue neuro-inflammation by acting as an anti-depressant. Our in vitro microglia cell culture data confirmed that recombinant omentin-1 suppresses microglial activation and pro-inflammatory cytokine expression induced by LPS. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of depression by providing a barrier-promoting effect and an endogenous anti-inflammatory balance to downregulate the proinflammatory cytokines.
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