Brain Structural and Functional Alterations in Mice Prenatally Exposed to LPS Are Only Partially Rescued by Anti-Inflammatory Treatment

Abstract

Aberrant immune activity during neurodevelopment could participate in the generation of neurological dysfunctions characteristic of several neurodevelopmental disorders (NDDs). Numerous epidemiological studies have shown a link between maternal infections and NDDs risk; animal models of maternal immune activation (MIA) have confirmed this association. Activation of maternal immune system during pregnancy induces behavioral and functional alterations in offspring but the biological mechanisms at the basis of these effects are still poorly understood. In this study, we investigated the effects of prenatal lipopolysaccharide (LPS) exposure in peripheral and central inflammation, cortical cytoarchitecture and behavior of offspring (LPS-mice). LPS-mice reported a significant increase in interleukin-1β (IL-1β) serum level, glial fibrillary acidic protein (GFAP)- and ionized calcium-binding adapter molecule 1 (Iba1)-positive cells in the cortex. Furthermore, cytoarchitecture analysis in specific brain areas, showed aberrant alterations in minicolumns’ organization in LPS-mice adult brain. In addition, we demonstrated that LPS-mice presented behavioral alterations throughout life. In order to better understand biological mechanisms whereby LPS induced these alterations, dams were treated with meloxicam. We demonstrated for the first time that exposure to LPS throughout pregnancy induces structural permanent alterations in offspring brain. LPS-mice also present severe behavioral impairments. Preventive treatment with meloxicam reduced inflammation in offspring but did not rescue them from structural and behavioral alterations.

Keywords

• maternal immune activation
• lipopolysaccharide
• anti-inflammatory drugs
• cortical structure
• behavior
• neurodevelopmental disorders