Dextromethorphan reduces prenatal lipopolysaccharide exposure-induced dopaminergic neuronal loss and cytokine changes in offspring

Chia Yu Huang, Sabrina Wang*

*此作品的通信作者

研究成果: Article同行評審

摘要

Maternal infection during pregnancy may affect fetal brain development and increase the risk of developing neurological and mental disorders later in life in offspring. In this study, we used low-dose lipopolysaccharide (LPS) injection to mimic mild maternal infection at a critical time window for fetal dopamine (DA) and serotonin (5-HT) neuron development. The affected offspring exhibited reduction of dopaminergic and serotonergic neurons and anxiety- and depression-related behaviors in adulthood. In the current study, we evaluated whether dextromethorphan (DM, 30 mg/kg), an over-the-counter antitussive drug with anti-inflammatory and neuroprotective properties, could reduce the adverse effects of maternal infection mimicked by LPS exposure. We discovered that DM application did not change the baseline serum interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) levels in the LPS-exposed offspring. However, DM treatment could reduce the heightened immune responses induced by a postnatal LPS challenge test in prenatal LPS-exposed offspring. The neuroprotective effect of DM was only seen in DA neurons but not in 5-HT neurons. We concluded that DM treatment can partially protect the offspring against the adverse effects of LPS-induced maternal immune activation. The reduction in heightened immune responses and dopaminergic neuronal loss in LPS-exposed offspring could potentially reduce the risk of DA-related neurological and psychiatric disorders later in life.

原文English
頁(從 - 到)261-270
頁數10
期刊International Journal of Developmental Neuroscience
82
發行號3
DOIs
出版狀態Published - 5月 2022

指紋

深入研究「Dextromethorphan reduces prenatal lipopolysaccharide exposure-induced dopaminergic neuronal loss and cytokine changes in offspring」主題。共同形成了獨特的指紋。

引用此