title: Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China. Electronic address: yao.zb@163.com.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000276:immunology / Q000517:prevention & control; D001500:BCG Vaccine; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4; D008297:Male; D018782:Maze Learning; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D009043:Motor Activity / Q000276:immunology; D055495:Neurogenesis / Q000276:immunology*; D065852:Spatial Memory
chemical_list: D001500:BCG Vaccine; D051792:Basic Helix-Loop-Helix Proteins; D007371:Interferon-gamma; D015847:Interleukin-4; C095572:Hand1 protein, mouse
keywords: Cytokine; Hippocampus; Microglia; Neurotrophin; Th bias; Vaccine