出生后免疫激活（PIA）可以影响正常的大脑发育，并增加以后生活中行为异常的风险，包括类似抑郁的行为.因此,迫切需要找到安全有效的PIA临床药物。最近,astilbin(ASB)在神经系统疾病中的保护作用备受关注。然而,ASB对神经发育疾病的影响尚不清楚.在这项研究中,我们使用脂多糖(LPS)诱导的PIA小鼠模型,发现ASB在成年小鼠中特异性改善PIA诱导的抑郁样行为,但不改善焦虑样行为.星形胶质细胞在调节神经炎症中起重要作用，是大脑中最丰富的细胞类型。在PIA模型中,我们发现ASB选择性抑制星形胶质细胞激活,但不抑制皮质和海马中的小胶质细胞激活.此外，我们的结果表明，ASB特异性上调menin蛋白在星形胶质细胞中的表达，并阻断P65蛋白进入细胞核，从而抑制星形胶质细胞分泌IL-1β和TNF-α。一起来看,ASB通过靶向menin减少星形胶质细胞介导的神经炎症的发生，从而减弱PIA诱导的抑郁样行为。我们的结果表明，ASB可能是一种有吸引力的抗抑郁药物，并在PIA中发挥抗抑郁作用。在药物选择方面，ASB可能是抑郁症状患者的特异性药物。
Postnatal immune activation (PIA) can affect normal brain development and increase the risk of behavioral abnormalities in later life, including depressive-like behavior. Therefore, there is an urgent need to find safe and effective clinical medications for PIA. Recently, the protective effect of astilbin (ASB) in nervous system diseases has attracted much attention. However, the effect of ASB on neurodevelopmental diseases remains unclear. In this study, we used a lipopolysaccharide (LPS)-induced PIA mouse model and found that ASB specifically improved PIA-induced depressive-like behavior but not anxiety-like behavior in adult mice. Astrocytes play an essential role in regulating neuroinflammation, and are the most abundant cell type in the brain. In the PIA model, we found that ASB selectively inhibited astrocyte activation but not microglial activation in the cortex and hippocampus. Moreover, our results showed that ASB specifically upregulated the expression of menin protein in astrocytes and blocked the entry of P65 protein into the nucleus, thus inhibiting the secretion of IL-1β and TNF-α by astrocytes. Taken together, ASB reduced the occurrence of astrocyte-mediated neuroinflammation by targeting menin, thereby attenuating the PIA-induced depressive-like behavior. Our results reveal that ASB may be an attractive antidepressant drug and exert an antidepressant effect in PIA. In terms of drug selection, ASB may be a specific drug for patients with depressive symptoms.
