An enriched environment restores hepatitis B vaccination-mediated impairments in synaptic function through IFN-γ/Arginase1 signaling

• Published in: Brain, behavior, and immunity behavior, and immunity, 2018-07, Vol.71, p.116-132
• Main Authors: Qi, Fangfang, Zuo, Zejie, Hu, Saisai, Xia, Yucen, Song, Dan, Kong, Jiechen, Yang, Yang, Wu, Yingying, Wang, Xiao, Yang, Junhua, Hu, Dandan, Yuan, Qunfang, Zou, Juntao, Guo, Kaihua, Xu, Jie, Yao, Zhibin
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Arginase - drug effects; Arginase - genetics; Complement; Cytokine; Cytokines; Enriched environment; Environment; Female; Hepatitis B; Hepatitis B Vaccines - adverse effects; Hippocampus; Hippocampus - drug effects; Interferon-gamma - drug effects; Interferon-gamma - genetics; Male; Maze Learning - physiology; Memory Disorders - immunology; Memory Disorders - physiopathology; Mice; Mice, Inbred C57BL; Microglia - immunology; Neurogenesis - immunology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Spatial Memory - drug effects; Th2 Cells - drug effects; Vaccination - adverse effects; Vaccine
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2018.04.003

•The enriched environment restores Hepatitis B vaccination-mediated impairments in synaptic function.•The enriched environment induced hippocampal microglial anti-inflammatory M2 polarization.•Knock-down of the Arginase1 gene prevented the effects of the enriched environment on restoring the dendritic spine density.•The EE prevents synapse loss induced by the HBV via regulation of complement protein expression. Activation of the neonatal immune system may contribute to deficits in neuronal plasticity. We have reported that neonatal vaccination with a hepatitis B vaccine (HBV) transiently impairs mood status and spatial memory involving a systemic T helper (Th) 2 bias and M1 microglial activation. Here, an EE induced microglial anti-inflammatory M2 polarization, as evidenced by selectively enhanced expression of the Arginase1 gene (Arg-1) in the hippocampus. Interestingly, knock-down of the Arg-1 gene prevented the effects of EE on restoring the dendritic spine density. Moreover, levels of the Th1-derived cytokine IFN-gamma (IFN-γ) were elevated in the choroid plexus (CP), which is the interface between the brain and the periphery. IFN-γ-blocking antibodies blunted the protective effects of an EE on spine density and LTP. Furthermore, levels of complement proteins C1q and C3 were elevated, and this elevation was associated with synapse loss induced by the HBV, whereas an EE reversed the effects of the HBV. Similarly, blockade of C1q activation clearly prevented synaptic pruning by microglia, LTP inhibition and memory deficits in hepatitis B-vaccinated mice. Together, the EE-induced increase in IFN-γ levels in the CP may disrupt systemic immunosuppression related to HBV via an IFN-γ/Arg-1/complement-dependent pathway.