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Brain Behav Immun. 2018 Jul;71:116-132. doi: 10.1016/j.bbi.2018.04.003. Epub 2018 Apr 5.

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

Author information

1
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
2
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China.
3
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China; Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, 232 Waihuandong Road, Guangzhou 510006, PR China.
4
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China; Department of Neurology, Guangzhou Women and Children's Hospital, #9, Jinsui Road, Guangzhou 510623, PR China.
5
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan No. 2 Road, Guangzhou 510080, PR China. Electronic address: yao.zb@163.com.

Abstract

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.

KEYWORDS:

Complement; Cytokine; Enriched environment; Hippocampus; Vaccine

PMID:
29627530
DOI:
10.1016/j.bbi.2018.04.003

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