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. We therefore hypothesized that neonatal LPS exposure might induce PFC ATP8A2 down-regulation by increasing IFN-γ level. Here, C57BL6/J mice of both sexes received 3-dose-injections of LPS (50μg/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-γ level. Using neutralizing mAb, IFN-γ was identified as the key mediator of LPS-induced PFC ATP8A2 decrease. Besides, neutralizing IFN-γ 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-γ level, maybe associated with mechanism underlying LPS-induced brain and behavior impairments.

中文翻译：

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新生儿LPS暴露可通过增加IFN-γ水平降低小鼠前额皮层ATP8A2水平

新生儿脂多糖（LPS）暴露会在涉及干扰素（IFN）-γ升高的啮齿类动物中引起抑郁样行为。研究已将前额叶皮质（PFC）ATPase磷脂转运8A2（ATP8A2）表达的下调与抑郁样行为联系起来。在非神经元细胞中，IFN-γ可以降低ATP8A2的表达。因此，我们假设新生儿LPS暴露可能通过增加IFN-γ水平而诱导PFC ATP8A2下调。在这里，男女C57BL6 / J小鼠在出生后（PND）5，PND7和PND9接受3剂LPS注射（50μg/ kg体重，腹腔注射）。LPS处理的小鼠显示PFC ATP8A2表达瞬时降低。此外，发现PFC ATP8A2表达与IFN-γ水平呈负相关。使用中和单克隆抗体，IFN-γ被确定为LPS诱导的PFC ATP8A2减少的关键介质。除了，新生儿LPS暴露期间中和IFN-γ可减轻成年期的抑郁样行为。总之，新生儿LPS暴露通过增加IFN-γ水平降低了小鼠PFC中的ATP8A2水平，这可能与LPS诱导的大脑和行为障碍的潜在机制有关。