Remodeling the Th1 polarized systemic environment contributes to neurogenesis and cognitive function via the Wnt7a pathway in neonatal mice.
Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum. This result indicated that the immune homeostatic milieu in postnatal mice was broken and the Th1 polarized systemic environment in the BCG-serum group was remodeled. The BCG-serum group displayed more BrdU+/DCX+cells, BrdU+/NeuN+cells, Nestin+cells and better cognitive abilities. In neural stem cells, the Wnt7a/β-catenin signaling pathway was activated and exposure to the Wnt7a antagonist Dickkopf-1 inhibited BCG-serum-induced Wnt7a/β-catenin signaling, neurogenesis and cognitive function. Additionally, BCG-serum was associated with elevations in hippocampal brain-derived neurotrophic factor (BDNF) levels, and BDNF expression in the BCG-serum group was offset by Dickkopf-1 treatment. By rebalancing the Th1 polarized systemic environment in neonatal mice, it is possible that treatment with BCG-serum promotes hippocampal neurogenesis and improves cognitive functions, which are associated with Wnt7a/β-catenin-BDNF signaling.
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China; South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
YunLong
Y
Xu
Department of Radiation Oncology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510080, PR China.
Fen
F
He
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China.
FangFang
F
Qi
Department of Radiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, PR China.
Guangqi
G
Yang
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China.
FuXiang
F
Zheng
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China.
JunHua
J
Yang
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China.
Xiao
X
Wang
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Sun Yat-Sun University, Guangzhou 510080, PR China. Electronic address: liujunxiu99@163.com.
JunXiu
J
Liu
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhongshan 2nd Road, Guangzhou 510080, PR China. Electronic address: zoujunt@mail.sysu.edu.cn.
JunTao
J
Zou
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C000714847:Dcx protein, mouse; C501127:Dkk1 protein, mouse; D000089662:Doublecortin Protein; D036341:Intercellular Signaling Peptides and Proteins; D015847:Interleukin-4; D007371:Interferon-gamma
BCG-serum; Cognitive function; Cytokine; Neurogenesis; T helper 1; Wnt7a signaling pathway