Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life
Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life
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新生小鼠 BCG 疫苗接种可改善早期神经发生和行为
DOI：
10.1016/j.brainresbull.2015.10.012
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发表时间：
2016-01-01
影响因子：
3.8
通讯作者：
Yao, Zhibin
中科院分区：
文献类型：
--
作者：
Yang, Junhua;Qi, Fangfang;Yao, Zhibin
卡介苗（BCG）在全世界范围内对新生儿进行接种，但尽管免疫系统与大脑密切相关，但这种新生儿疫苗接种是否会影响出生后早期的大脑发育仍不清楚。新生C57BL/6小鼠皮下注射卡介苗或磷酸盐缓冲盐水(PBS)，并在4周和8周龄时观察其情绪状态和空间认知。还在第 2 周和第 6 周时对小鼠进行了测试，以检查卡介苗对神经发生、海马小胶质细胞表型和数量以及海马神经免疫分子和外周细胞因子表达的影响。注射 BCG 的小鼠在 4 周时表现出更好的行为表现。我们观察到神经发生、M2 小胶质细胞活化和神经免疫分子的神经营养特征增加[更多的干扰素 (IFN)-γ、白细胞介素 (IL)-4、转化生长因子 (TGF)-β、脑源性神经营养因子 (BDNF) 和胰岛素样生长因子 (IGF)-1 和更少的肿瘤坏死因子 (TNF)-α。 2 周龄 BCG 小鼠海马体中的 IL-1 β 和 IL-1 β。在外周，BCG 诱导 T 辅助细胞 (Th)-1 血清反应。在个体水平上，血清IFN-γ/IL-4比值与神经营养素水平和海马神经发生呈正相关。这些发现表明，新生儿 BCG 疫苗接种通过影响大脑中的神经免疫环境，改善了早期生命中的神经发生和小鼠行为，这可能与系统性 Th1 偏好有关。 (C) 2015 Elsevier Inc. 保留所有权利。
Bacillus Calmette-Guerin (BCG) is administered to neonates worldwide, but it is still unknown whether this neonatal vaccination affects brain development during early postnatal life, despite the close association of the immune system with the brain. Newborn C57BL/6 mice were injected subcutaneously with BCG or phosphate-buffered saline (PBS) and their mood status and spatial cognition were observed at four and eight weeks (w) old. The mice were also subjected to tests at 2 and 6 w to examine BCG's effects on neurogenesis, the hippocampal microglia phenotype and number, and the expression of hippocampal neuroimmune molecules and peripheral cytokines. The BCG-injected mice showed better behavioral performances at 4 w. We observed elevated neurogenesis, M2 microglial activation and a neurotrophic profile of neuroimmune molecules [more interferon (IFN)-gamma, interleukin (IL)-4, transforming growth factor (TGF)-beta, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1 and less tumor necrosis factor (TNF)-alpha. and IL-1 beta in the hippocampus of the 2-w-old BCG-mice. In the periphery, BCG induced a T helper (Th)-1 serum response. At the individual level, there were positive correlations between the serum IFN-gamma/IL-4 ratio and the levels of neurotrophins and neurogenesis in the hippocampus. These findings suggest that neonatal BCG vaccination improved neurogenesis and mouse behavior in early life by affecting the neuroimmune milieu in the brain, which may be associated with a systemic Th1 bias. (C) 2015 Elsevier Inc. All rights reserved.