Yang Junhua, Qi Fangfang, Gu Huaiyu, Zou Juntao, Yang Yang, Yuan Qunfang, Yao Zhibin
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
Brain Res Bull. 2016 Jan;120:25-33. doi: 10.1016/j.brainresbull.2015.10.012. Epub 2015 Nov 1.
Bacillus Calmette-Guérin (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)-γ, interleukin (IL)-4, transforming growth factor (TGF)-β, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1 and less tumor necrosis factor (TNF)-α and IL-1β] 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-γ/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.
卡介苗（BCG）在全球范围内用于新生儿接种，但尽管免疫系统与大脑密切相关，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。给新生的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周龄时观察它们的情绪状态和空间认知能力。还在2周和6周时对小鼠进行测试，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。注射卡介苗的小鼠在4周时表现出更好的行为表现。我们观察到，2周龄卡介苗接种小鼠海马中的神经发生增加、M2小胶质细胞活化以及神经免疫分子的神经营养谱[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，更少的肿瘤坏死因子（TNF）-α和IL-1β]。在周围组织中，卡介苗诱导了辅助性T（Th）-1血清反应。在个体水平上，血清IFN-γ/IL-4比值与海马中神经营养因子水平和神经发生之间存在正相关。这些发现表明，新生儿接种卡介苗通过影响大脑中的神经免疫环境改善了早期生活中的神经发生和小鼠行为，这可能与全身性Th1偏向有关。
