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.
|Number of pages
|International Journal of Developmental Neuroscience
|Published - May 2022