Prenatal zinc supplementation ameliorates hippocampal astrocytes activation and inflammatory cytokines expression induced by lipopolysaccharide in a rat model of maternal immune activation

Objective: There is evidence that gestational exposure to lipopolysaccharide (LPS) results in fetal zinc deficiency, and eventually neurodevelopmental abnormalities. In this study, we utilized a rat model of maternal immune activation (MIA) to investigate the possible neuroprotective effect of zinc supplementation throughout pregnancy on hippocampal astrocytes activation as well as inflammatory cytokines expression in adult offspring. Methods: Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline at gestational day (GD) 15 and 16 and orally gavaged with zinc sulfate (30 mg/kg) throughout pregnancy. Astrocyte density and histological assessment were evaluated in the hippocampus of adult offspring at postnatal day (PND) 60-62. Also, the mRNA levels of IL-6, TNF-α, IL-1β, NF-κB, and glial fibrillary acidic protein (GFAP) were measured using qPCR analysis. Results: Prenatal exposure to LPS resulted in up-regulated expression levels of IL-6, TNF-α, NF-κB, and GFAP in the hippocampus of adult pups. Moreover, offspring from LPS group showed an increased astrocyte density in CA1 region with no histological alterations in CA1 and CA3 areas. Conversely, maternal zinc supplementation ameliorated these inflammatory alterations induced by LPS. Discussion: This study provides support for the premise that zinc supplementation during pregnancy might be an early treatment option to inhibit hippocampal inflammation induced by the maternal immune response to infectious agents.