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bioRxiv · 10.1101/2020.08.09.243477

Neonatal LPS exposure results in ATP8A2 down-regulation in the prefrontal cortex and depressive-like behaviors in mice through increasing IFN-γ level

Deng, J.·Song, L.·Yang, Z.·Zheng, S.·Du, Z.·Luo, L.·Liu, J.·Jin, X.·Yang, J.
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Abstract

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.

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Deng, J., Song, L., Yang, Z., Zheng, S., Du, Z., Luo, L., Liu, J., Jin, X., Yang, J.. 2020-08-10. Neonatal LPS exposure results in ATP8A2 down-regulation in the prefrontal cortex and depressive-like behaviors in mice through increasing IFN-γ level. https://doi.org/10.1101/2020.08.09.243477

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