Neonatal vaccination with bacillus Calmette-Guérin and hepatitis B vaccines modulates hippocampal synaptic plasticity in rats

•Neonatal BCG vaccination enhances hippocampal synaptic plasticity in rats.•Neonatal HBV vaccination impaired hippocampal synaptic plasticity in rats.•Vaccinated combined with BCG and HBV has no influence on synaptic plasticity.•BCG induced a Th1 immune response and HBV induced a Th2 response in periphery.•Peripheral Th1/Th2 bias was positively correlated with BDNF and IGF-1 in hippocampus.

Immune activation can exert multiple effects on synaptic transmission. Our study demonstrates the influence of neonatal vaccination on hippocampal synaptic plasticity in rats under normal physiological conditions. The results revealed that neonatal BCG vaccination enhanced synaptic plasticity. In contrast, HBV hampered it. Furthermore, we found that the cytokine balance shifted in favour of the T helper type 1/T helper type 2 immune response in BCG/HBV-vaccinated rats in the periphery. The peripheral IFN-γ:IL-4 ratio was positively correlated with BDNF and IGF-1 in the hippocampus. BCG raised IFN-γ, IL-4, BDNF and IGF-1 and reduced IL-1β, IL-6, and TNF-α in the hippocampus, whereas, HBV triggered the opposite effects.

Graphical abstractOur findings support the hypothesis that neonatal vaccination with BCG or HBV modulates hippocampal synaptic plasticity probably via the neuro-beneficial or neuro-detrimental expression profiles of hippocampal cytokines and neurotrophins. BCG vaccination facilitated the induction of hippocampal LTP, increased the spine density and area, elicited a selective increase in mushroom spines in the hippocampal DG area, and elevated hippocampal synaptophysin, PSD-95, and NMDAR2A protein levels. Conversely, HBV vaccination showed almost inverse alterations of all these aspects. In this study, BCG induced a Th1-like response followed by increased neurotrophins in the brain, whereas HBV induced a Th2-like response followed by decreased neurotrophins. In addition, positive correlations between the IFN-γ:IL-4 ratio and BDNF and IGF-1 were observed. Interestingly, BH showed no obvious shift to either a Th1 or Th2 response and no significant influence on synaptic plasticity.Download high-res image (118KB)Download full-size image