Neonatal LPS exposure reduces ATP8A2 level in the prefrontal cortex in mice via increasing IFN-γ level

Abstract

Neonatal lipopolysaccharide (LPS) exposure can cause depressive-like behaviors in rodents involving elevated interferon (IFN)-γ. Studies have linked down-regulation of prefrontal cortex (PFC) ATPase phospholipid transporting 8A2(ATP8A2) expression to depressive-like behaviors. In non-neuronal cells, IFN-γ could reduce ATP8A2 expression. Therefore, we hypothesized that neonatal LPS exposure might induce PFC ATP8A2 down-regulation by increasing the IFN-γ level. Here, C57BL6/J mice of both sexes received 3-dose-injections of LPS (50 μg/kg body weight, i.p.) on postnatal day (PND)5, PND7, and PND9. LPS-treated mice showed a transiently decreased PFC ATP8A2 expression indicated by western blot results. Moreover, a significant negative correlation of PFC ATP8A2 expression was found with the IFN-γ level. Using neutralizing mAb, IFN-γ was identified as the key mediator of LPS-induced PFC ATP8A2 decrease indicated by western blot and immunofluorescence results. In sum, neonatal LPS exposure reduced ATP8A2 level in PFC in mice via increasing IFN-γ level. This finding may help further understand the mechanism underlying LPS-induced impairments in brain development and function.

Keywords: Brain; Cytokine; Immune activity; P4-ATPase.