Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

Abstract

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation.

Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring

“…Consistent with previous findings from our laboratory, polyI:C treatment reduced maternal weight in Long Evans rats (Ballendine et al 2015;Howland et al 2012;Paylor et al 2016;Sangha et al 2014;Zhang et al 2012). Others have reported that maternal weight is not consistently reduced following polyI:C administration in Sprague Dawley rats (Bronson et al 2011;Wolff and Bilkey 2010) and that weight loss was observed in Wistar rats for roughly a day, although the magnitude of loss was not quantified (Zuckerman et al 2003;Zuckerman and Weiner 2005). Maternal temperature changes in response to polyI:C administration are inconsistent in our laboratory (Ballendine et al 2015;Howland et al 2012;Sangha et al 2014;Zhang et al 2014).…”

Behavioral alterations in rat offspring following maternal immune activation and ELR-CXC chemokine receptor antagonism during pregnancy: Implications for neurodevelopmental psychiatric disorders

“…Consideration of these data along with the PPI data suggests that this group of offspring was more mildly affected by polyI:C treatment. While the specific factors that led to this pattern of results are unclear, others have noted that body weight change in the dams following polyI:C treatment is predictive of the phenotype of the offspring (Bronson et al, 2011). Since the body weight changes observed in the dams following polyI:C treatment are of a similar initial magnitude between this data set and the other studies from our group Sangha et al, 2014;Zhang et al, 2012), other non-specific factors may have contributed.…”

Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring

“…Animals were housed under standard conditions with access to food and water ad libitum . The Poly I:C treatment protocol was performed as previously described (Bronson et al, 2011; Hemmerle et al, 2015). Briefly, on gestational day 14 pregnant dams were injected with Poly I:C (8 mg/kg i.p.…”