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Non-infectious maternal fever impairs sociability in rat offspring
Abstract Number: F5A-1
Abstract Type: Original Research
Background: Maternal fever is common in pregnancy; twenty percent of pregnant US women report one or more fever episodes (1). Fever during pregnancy may raise the risk for autism spectrum disorder in the child (2). We previously observed fetal neuroinflammation following non-infectious maternal fever (3) but the effect on rat offspring behavior remains unknown. We tested the hypothesis that non-infectious maternal fever affects social behavior in rat offspring.
Methods: Following isoflurane anesthetic, 12 pregnant rats were implanted with intracerebroventricular (i.c.v.) catheters on GD14. Rats were later injected on GD20 with either saline (n=6) or systemic IL-6 injections (1µg, 1.5 µg and 4.5 µg, q 30 min) + one-time i.c.v. PGE1 0.2 µg administration (n=6) at time 0. Core temperature was recorded. One to two days post injection, dams delivered vaginally. Sixteen pups (n=8/group) whose mothers were exposed to saline (control) or IL 6- PGE1 (test) were weaned and tested at age eight weeks for Crawley's sociability three chamber test. Sociability was defined as the propensity to spend time with another rat, as compared to time spent alone in an identical but empty chamber; observers were blinded to the experimental condition. Repeated measures ANOVA were used to compare core temperatures. Student t-test was used to compare the time difference spent in different chambers between subjects. Data are presented as Mean ± SEM. P<0.05 was considered statistically significant.
Results: Injection of rat IL-6 + PGE1 produced an elevation of 1 ± 0.2 ºC maternal temperature in the first hour compared to vehicle (P<0.001). Control offspring preferentially sniffed the enclosure containing the stranger rat when compared to offspring whose mothers had non-infectious fever (56 ± 4.2 vs 36 ± 5.3 seconds respectively, P= 0.015). Control offspring also spent more time with a novel rat than with the empty cup (56 ± 4.2 vs 13 ± 5.6 seconds respectively, P<0.001). Conversely, offspring whose mother had exposure to IL-6 and PGE1 showed no social preference for either side (Fig. 1).
Discussion: For rodents, recognition of and interaction with conspecifics is a social behavior that is important for maintaining social hierarchy and for mate choice. These preliminary results show a pattern of impaired social behavior in the offspring of rats exposed to fever during pregnancy. Further work is required to assess the impact of non-infectious fever on offspring social development.