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Dose-dependent sickness behavior,abortion and inflammation induced by systemic LPS injection in pregnant mice
Authors:Rovana Paludo Toyama  João Carlos Xikota  Marcelo L. Schwarzbold  Tania Silvia Frode  Ziliani da Silva Buss  Jean Costa Nunes
Affiliation:1. Laboratory of Nutrology and Metabology (MENULAB), Florianopolis, SC, Brazil,;2. Postgraduation Program in Medical Sciences, UFSC, Florianopolis, SC, Brazil,;3. Postgraduation Program in Medical Sciences, UFSC, Florianopolis, SC, Brazil,;4. Department of Pedriatics, Federal University of Santa Catarina (UFSC), Florianopolis, SC, Brazil,;5. Interdisciplinary Center for Human Development (Desenvolver Center) of the undergraduate course of Medicine, Mother-Child Healthcare System, UNISUL, Brazil,;6. Department of Medical Clinic, Hospital Universitário (HU)/UFSC, Center of Clinical and Experimental Neurology, Florianopolis, SC, Brazil,;7. Postgraduation Program in Medical Sciences, UFSC, Florianopolis, SC, Brazil,;8. Postgraduation Program in Medical Sciences, UFSC, Florianopolis, SC, Brazil,;9. Anatomopathology Service, HU, UFSC, Florianopolis, SC, Brazil,;10. Center of Applied Neurosciences (CeNAp), HU, UFSC, Florianopolis, SC, Brazil, and;11. Hospital Governador Celso Ramos (HGCR), Epilepsy Center of Santa Catarina (CEPESC), Florianopolis, SC, Brazil
Abstract:Objective: Clinical and experimental evidences indicate that intrauterine inflammation during pregnancy is associated to brain damage. The objective of this study is to determine the effects of lipopolysaccharide in temperature, cytokine production and sickness behavior of pregnant dams.

Methods: A single i.p. injection of lipopolysaccharide (LPS) (50, 150 or 300?µg/kg) was administered on E18. Controls received isotonic saline. Body temperature was controlled before and 3?h after injections. Animals’ behavior was assessed by the OF test 3?h following treatment. Animals were sacrificed for leukocyte, IL-1β and TNF-α determination. Placental tissue and abortion were also examined.

Results: LPS administration elicited hypothermia. Abortion was observed in LPS 150 and 300?µg/kg. Leukocyte levels were significantly lower with LPS 300?µg/kg than in controls. LPS induced dose-dependent impairment in animals’ locomotion. IL-1β serum and amniotic fluid were higher than the saline, and TNF-α serum and amniotic fluid increased when compared to controls. Placental histopathologic abnormality was not found.

Conclusion: LPS induces dose-dependent sickness behavior and hypothermia in pregnant mice. Our findings suggest that the presence of inflammation may be a causative factor for premature labor and that Escherichia coli antigens modify the concentration of pro-inflammatory agents in circulatory system and intra-uterine environment.

Keywords:Body temperature  lipopolysaccharide  locomotion  sickness behavior
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