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. 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.

Cow's milk αS1-casein is more sensitizing than goat's milk αS1-casein in a mouse model

“…41 Although LPS induced the release of IFN-γ by NK cells and the release of pro-inflammatory cytokines, including IFN-γ, IL-1 and IL-6 have been reported, LPS may play roles in allergy, which is not clear. 42 LPS, also known as endotoxin, is the main component of the outer membrane of the cell wall of Gram-negative bacteria. It is released by lysis of Gram-negative bacteria in the intestine and is a key factor in inducing systemic inflammatory reactions.…”

Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors

“…The cytokines assays were conducted according to the method provided in previous literature [34, 41–44].…”

“…The mice were anesthetized with an overdose of 2% pentobarbital sodium (Merck Co. Ltd, Shanghai, China) [41] and blood samples were collected from the heart immediately [42]. The blood was coagulated at room temperature for 30 min and then centrifuged (4000 g , 4 °C) for 10 min [34].…”

“…The calculation of sucrose preference is shown in the formula below. The cytokines assays were conducted according to the method provided in previous literature [34,[41][42][43][44].…”

Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF

“…In addition to causing inflammation of the lungs and airways, allergic asthma can also induce strong immune activation in the brain during critical the stage of brain development, indicated by significant increase of pro-inflammatory cytokines IL-1β, IL-6, and TNF in the hippocampus and prefrontal cortex. Allergic asthma patients, therefore, are potential neuroinflammation sufferers and may develop into some nervous system diseases or mental diseases (Antunes et al 2022 ; Duan et al 2018 ; Han et al 2018 ; Xia et al 2014 ). A study by Smith et al reported upregulated expression of the pro-inflammatory factor TNF and the activation of astrocytes in the brain of milk-allergic mice while exhibiting pronounced anxiety and depression-like behavior (Smith et al 2019 ).…”