Prenatal Zinc Supplementation Improves Working Memory Impairment and Inflammatory Response in LPS-Induced Maternal Immune Activation Model
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Introduction: Maternal exposure to infectious agents such as lipopolysaccharide (LPS) is known as a significant environmental risk factor which increases the risk of schizophrenia or other neurodevelopmental disorders in the next generation. Due to the prominent role of zinc in the brain function and more importantly a recent evidence indicating the association between gestational exposure to LPS and fetal zinc deficiency, in the present study, we utilized maternal LPS injection as a model for schizophrenia to investigate whether zinc supplementation can prevent LPS-associated alterations. Material and method: On gestation day (GD) 15 and 16, pregnant dams received intraperitoneal injection of either LPS (500µg/kg) or vehicle and supplemented with ZnSO4 (30mg/kg) throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to assess working memory of the male offspring. Besides, the expression levels of pro-inflammatory mediators including tumor necrosis factor α (TNFα), IL-1β, and IL-6 were evaluated in the frontal cortex of male pups using qPCR. Iba1 immunostaining for microglia was also carried out on the brain sections. Results: Male offspring born to LPS-treated dams exhibited significantly increased mRNA levels of TNFα, IL-1β, IL-6, and microglial activity as well as impairment in working memory. However, maternal zinc supplementation could alleviate microglial activation and cytokine production in the frontal cortex of LPS-exposed pups. Furthermore, zinc treatment led to an improvement in the working memory of prenatally LPS-treated offspring to a level comparable to those measured in vehicle-treated offspring. Conclusion: These findings support the idea that the deleterious effects of prenatal LPS exposure could be attenuated by zinc supplementation during pregnancy.
Authors and Affiliations
Ronak Mousavian, Nahid Davoodian, Ebrahim Savare, Faezeh Alizadeh, Haniyeh Kazemi
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