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

Neonatal lipopolysaccharide (LPS) exposure can cause depressive-like behaviors in rodents involving elevated interferon (IFN)-{gamma}. Studies have linked down-regulation of prefrontal cortex (PFC) ATPase phospholipid transporting 8A2(ATP8A2) expression to depressive-like behaviors. In non-neuronal cells, IFN-{gamma} could reduce ATP8A2 expression. We therefore hypothesized that neonatal LPS exposure might induce PFC ATP8A2 down-regulation by increasing IFN-{gamma} level. Here, C57BL6/J mice of both sexes received 3-dose-injections of LPS (50g/kg bodyweight, i.p.) on postnatal day (PND)5, PND7 and PND9. LPS-treated mice showed a transiently decreased PFC ATP8A2 expression. Moreover, a negative correlation of PFC ATP8A2 expression was found with IFN-{gamma} level. Using neutralizing mAb, IFN-{gamma} was identified as the key mediator of LPS-induced PFC ATP8A2 decrease. Besides, neutralizing IFN-{gamma} during neonatal LPS exposure attenuated the depressive-like behaviors in adulthood. In sum, neonatal LPS exposure reduced ATP8A2 level in PFC in mice via increasing IFN-{gamma} level, maybe associated with mechanism underlying LPS-induced brain and behavior impairments.