期刊
BRAIN RESEARCH BULLETIN
卷 120, 期 -, 页码 25-33出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2015.10.012
关键词
Vaccine; Th bias; Cytokine; Neurotrophin; Hippocampus; Microglia
资金
- National Natural Science Foundation of China [31371130]
- Special Foundation of the Education Department of Guangdong Province
- Medical Scientific Research Foundation of Guangdong Province [2013-159]
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.
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