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Updated: Nov 11, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Neonatal LPS exposure reduces ATP8A2 level in the prefrontal cortex in mice via increasing IFN-γ level
Jiapeng Deng1, Linyang Song2, Zhiqin Yang3
1School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Insights
Neonatal exposure to lipopolysaccharide (LPS) decreased prefrontal cortex (PFC) ATP8A2 expression in mice. This reduction was mediated by increased interferon-gamma (IFN-γ) levels, potentially impacting brain development.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Neonatal lipopolysaccharide (LPS) exposure is linked to depressive-like behaviors and elevated interferon-gamma (IFN-γ).
- Down-regulation of prefrontal cortex (PFC) ATPase phospholipid transporting 8A2 (ATP8A2) expression is associated with depressive-like behaviors.
- IFN-γ can decrease ATP8A2 expression in non-neuronal cells.
Purpose of the Study:
- To investigate if neonatal LPS exposure induces PFC ATP8A2 down-regulation via increased IFN-γ levels.
- To elucidate the role of IFN-γ in mediating LPS-induced changes in PFC ATP8A2 expression.
Main Methods:
- C57BL6/J mice received three LPS injections on postnatal days 5, 7, and 9.
- Western blot analysis was used to assess PFC ATP8A2 expression.
- Neutralizing monoclonal antibodies (mAb) against IFN-γ were employed to determine its mediating role.
Main Results:
- LPS-treated mice exhibited transiently decreased PFC ATP8A2 expression.
- A significant negative correlation was observed between PFC ATP8A2 expression and IFN-γ levels.
- IFN-γ was confirmed as the key mediator of LPS-induced PFC ATP8A2 reduction.
Conclusions:
- Neonatal LPS exposure reduces PFC ATP8A2 levels in mice by increasing IFN-γ.
- This mechanism may contribute to understanding LPS-induced impairments in brain development and function.
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.
