Abstract
Several studies have indicated that inflammation during pregnancy increases the risk for the development of neuropsychiatric disorders in the offspring. Morphological brain abnormalities combined with deviations in the inflammatory status of the brain can be observed in patients of both autism and schizophrenia. It was shown that acute infection can induce changes in maternal cytokine levels which in turn are suggested to affect fetal brain development and increase the risk on the development of neuropsychiatric disorders in the offspring. Animal models of maternal immune activation reproduce the etiology of neurodevelopmental disorders such as schizophrenia and autism. In this study the poly (I:C) model was used to mimic viral immune activation in pregnant mice in order to assess the activation status of fetal microglia in these developmental disorders. Because microglia are the resident immune cells of the brain they were expected to be activated due to the inflammatory stimulus. Microglial cell density and activation level in the fetal cortex and hippocampus were determined. Despite the presence of a systemic inflammation in the pregnant mice, there was no significant difference in fetal microglial cell density or immunohistochemically determined activation level between the control and inflammation group. These data indicate that activation of the fetal microglial cells is not likely to be responsible for the inflammation induced deficits in the offspring in this model.
Highlights
Schizophrenia and autism are neurodevelopmental disorders that can arise early during postnatal life
We show that poly (I:C)-induced Maternal immune activation (MIA) does not affect microglial density and activation level during embryonic development suggesting that pathological activation of embryonic microglial cells at the onset of their colonization processes cannot explain neurological deficits observed at postnatal stages in offspring after poly (I:C)induced MIA
We focused our analysis on the cerebral cortex area located dorsally to the lateral ganglionic eminences (LGE) and medial ganglionic eminences (MGE), containing the frontal and pariental cortex on E11.5 and E12.5, and the somatosensory and motor cortex at E17.5
Summary
Schizophrenia and autism are neurodevelopmental disorders that can arise early during postnatal life. To study the mechanisms behind this association several animal models were developed in which pregnant rodents were infected with the influenza virus, polyinosinic:polycytidylic acid [poly (I:C)] or Immune activation and embryonic microglia lipopolysaccharide (LPS) (Patterson, 2009) These models confirmed that prenatal infection leading to MIA can lead to behavioral and neurological disorders in the offspring (Shi et al, 2003; Meyer et al, 2006; Fortier et al, 2007; Lowe et al, 2008; Harvey and Boksa, 2012; Giovanoli et al, 2013; Squarzoni et al, 2014). This was not observed when maternal poly (I:C) challenge was performed at mid gestation stage (E9; Meyer et al, 2006), a developmental age at which immature microglia, the resident immune cells of the brain, have not yet invaded the fetal central nervous system (CNS; Ginhoux et al, 2010; Rigato et al, 2011; Swinnen et al, 2013)
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