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Effect of maternal immune activation on pre‐ and postnatal murine brain development
Author(s) -
McDermott Kieran,
Pakan Janelle,
O'Loughlin Elaine
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb32
Subject(s) - microglia , offspring , inflammation , neuroinflammation , fetus , hippocampal formation , immune system , astrocyte , cytokine , lipopolysaccharide , medicine , central nervous system , immunology , biology , endocrinology , pregnancy , genetics
Prenatal inflammation is considered a risk factor for neurodevelopmental disorders such as autism and schizophrenia. Models of maternal inflammation have been developed to study the cellular alterations in the fetal brain following challenge with agents such as lipopolysaccharide (LPS). Studies suggest that some gestation periods have higher risk for developmental abnormalities after such immune activation and different brain regions are populated by neurones and glia at different times. This study investigated the effect of early immune activation on development of the fetal and postnatal brain. Time mated c57BL/6 mice were used. On embryonic day 12 (E12), mice received either a single injection of LPS ( 50 μg/kg) or saline. Tissue was collected at prenatal and postnatal ages and used to investigate effects on the developing hippocampal and amygdalar brain structures. qPCR was carried out on placental and brain samples for relevant pro‐inflammatory cytokines. Immunohistochemistry was performed for astrocyte (GFAP), microglia (IBA‐1) and neuronal (DCX, Nestin) markers. Cresyl violet staining was used to investigate structural integrity. qPCR results showed altered pro‐inflammatory placental cytokine profile and altered cytokine profile in the pre‐and postnatal brain. The glial and neuronal environment was also altered in offspring of LPS treated mice. This preliminary data has shown that a single injection of a bacterial mimetic can have diverse effects on the neurodevelopmental process. This study found that a single low dose of LPS administered at E12 induces pro‐inflammatory cytokines which may lead to structural changes in the prenatal brain which, potentially, may persist in the adult brain.