Immune stress in late pregnant rats decreases length of gestation and fecundity, and alters later cognitive and affective behaviour of surviving pre-adolescent offspring

Abstract

Immune challenge during pregnancy is associated with preterm birth and poor perinatal development. The mechanisms of these effects are not known. 5α-Pregnan-3α-ol-20-one (3α,5α-THP), the neuroactive metabolite of progesterone, is critical for neurodevelopment and stress responses, and can influence cognition and affective behaviours. To develop an immune challenge model of preterm birth, pregnant Long–Evans rat dams were administered lipopolysaccharide [LPS; 30 μg/kg/ml, intraperitoneal (IP)], interleukin-1β (IL-1β; 1 μg/rat, IP) or vehicle (0.9% saline, IP) daily on gestational days 17–21. Compared to control treatment, prenatal LPS or IL-1β reduced gestational length and the number of viable pups born. At 28–30 days of age, male and female offspring of mothers exposed to prenatal IL-1β had reduced cognitive performance in the object recognition task compared to controls. In females, but not males, prenatal IL-1β reduced anxiety-like behaviour, indicated by entries to the centre of an open field. In the hippocampus, progesterone turnover to its 5α-reduced metabolites was lower in prenatally exposed IL-1β female, but not in male offspring. IL-1β-exposed males and females had reduced oestradiol content in hippocampus, medial prefrontal cortex and diencephalon compared to controls. Thus, immune stress during late pregnancy reduced gestational length and negatively impacted birth outcomes, hippocampal function and central neurosteroid formation in the offspring.

Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries

“…However, such early intervention is limited in humans due to the lack of sensitive antenatal diagnostic tools to detect fetal conditions needing treatment. The present study opens new avenues for postnatal treatment aiming to protect against the effects of prenatal exposure to inflammation, an important risk factor now increasingly associated with several neurodevelopmental diseases (Boksa, 2010;Crampton et al, 2011;Girard et al, 2010b;Meyer, 2011;Paris et al, 2011;Stolp et al, 2011). Postnatal treatment would be a possible option in human neonates since diagnosis is easier after birth; for example through immediate postnatal placental evaluation.…”

Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

“…Moreover, Crhr2 mRNA expression is reduced in the basomedial amygdala (BMA) in prenatally stressed males (Fig. 3) and increased in the BMA in prenatally stressed females (Brunton et al 2011). This differential CRH receptor mRNA expression in the amygdaloid complex in prenatally stressed males and females may underlie the difference in anxiety-like behaviour following social stress exposure in late gestation.…”

“…The activation of the type 1 receptor (CRH-R1) mediates HPA axis responses and anxiety-like behaviours, whereas that of the type 2 receptor (CRH-R2) mediates the anxiolytic actions of urocortins 2 and 3 (Bale & Vale 2004). The expression of mRNA for the two CRH receptors is altered by prenatal social stress, and importantly there are distinct sex differences (Brunton et al 2011). In prenatally stressed males, but not in females, Crhr1 mRNA levels are greater in the CeA and basolateral amygdala than in those in unstressed controls (Brunton et al 2011; Fig.…”

Pregnancy risk factors in autism: a pilot study with artificial neural networks

“…Thirty-day-old experimental rats demonstrated low exploratory activity in the plus-maze test. Moreover, offspring rats of mothers exposed to stress during pregnancy show that interleukin-1β exposure had reduced estradiol content in hippocampus, medial prefrontal cortex, and diencephalon (31). The precise neurobiological mechanisms of action underlying these phenomena remain unknown.…”