Brain Structural and Functional Alterations in Mice Prenatally Exposed to LPS Are Only Partially Rescued by Anti-Inflammatory Treatment.
Francesca AriaSara Anna BoniniValentina CattaneoMarika PremoliAndrea MastinuGiuseppina MaccarinelliMaurizio MemoPublished in: Brain sciences (2020)
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.
Keyphrases
- inflammatory response
- anti inflammatory
- lps induced
- high fat diet induced
- white matter
- high fat diet
- oxidative stress
- insulin resistance
- adipose tissue
- pregnant women
- metabolic syndrome
- induced apoptosis
- cell death
- body mass index
- small molecule
- young adults
- signaling pathway
- binding protein
- early onset
- high resolution
- endoplasmic reticulum stress
- newly diagnosed
- cell cycle arrest
- amino acid