Abstract
The aim of our study was to investigate the brain-specific epigenetic effects on global enzymatic histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity after prenatal exposure to maternal immune challenge by polyinosinic:polycytidylic acid (Poly I:C) at gestational day (GD) 17 in C57BL/6JRccHsd mouse offspring. Pregnant mice were randomly divided into 2 groups, receiving either 5 mg/kg Poly I:C or phosphate buffered saline (PBS) intravenously at GD 17. Subsequently, the effects on whole brain enzymatic HDAC and DNMT activity and the protein levels of various HDAC isoforms were assessed in the offspring. Overall, a significant sex × treatment interaction effect was observed after prenatal exposure to maternal immune challenge by Poly I:C, indicative of increased global HDAC activity particularly in female offspring from mothers injected with Poly I:C when compared to controls. Results on the levels of specific HDAC isoforms suggested that neither differences in the levels of HDAC1, HDAC2, HDAC3, HDAC4 or HDAC6 could explain the increased global HDAC activity observed in female Poly I:C offspring. In conclusion, we show that Poly I:C administration to pregnant mice alters global brain HDAC, but not DNMT activity in adult offspring, whereas it is still unclear which specific HDAC(s) mediate(s) this effect. These results indicate the necessity for further research on the epigenetic effects of Poly I:C.
Highlights
Infection during pregnancy and its associated maternal immune response may negatively impact upon offspring brain development [1, 2], thereby increasing the risk to develop psychopathology later in life [3, 4]
A significant sex 9 treatment interaction effect was observed after prenatal exposure to maternal immune challenge by polycytidylic acid (Poly I):C, indicative of increased global histone deacetylase (HDAC) activity in female offspring from mothers injected with Poly I:C when compared to controls
Results on the levels of specific HDAC isoforms suggested that neither differences in the levels of HDAC1, HDAC2, HDAC3, HDAC4 or HDAC6 could explain the increased global HDAC activity observed in female Poly I:C offspring
Summary
Infection during pregnancy and its associated maternal immune response may negatively impact upon offspring brain development [1, 2], thereby increasing the risk to develop psychopathology later in life [3, 4]. The exact mechanisms by which prenatal maternal inflammation impacts upon offspring brain development remain to be elucidated though. Moderate to severe cell loss was observed in the adult hippocampal CA1, CA3 and dentate gyrus after prenatal maternal exposure to Poly I:C [11]. As Poly I:C is known to induce a short-lasting immune response, the timing of the maternal inflammatory response can be accurately linked to specific windows during foetal
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