Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5043169 | Neurobiology of Learning and Memory | 2017 | 12 Pages |
â¢BCG-serum induces a Th1 polarized systemic environment in neonatal mice.â¢Remodeling Th1 polarized systemic environment improves hippocampal neurogenesis and cognitive function.â¢Remodeling Th1 polarized systemic environment activates canonical Wnt7a/β-catenin signaling pathway in hippocampus.â¢Remodeling Th1 polarized systemic environment elevates hippocampal BDNF levels implicated in hippocampal neurogenesis.â¢The effect induced by remodeling Th1 polarized systemic environment can be prevented by DKK1 in BCG-serum 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.