Prenatal lipopolysaccharide increases maternal behavior, decreases maternal odor preference, and induces lipopolysaccharide hyporesponsiveness.

Sandra Penteado,Michelli Acenjo,Thiago Reis-Silva,Rafael César De Melo,Maria Martha Bernardi,Thiago Kirsten,Nicolle Queiroz-Hazarbassanov,Cristina De Oliveira Massoco-Salles Gomes

doi:10.3922/j.psns.2013.1.06

Abstract

The present study investigated whether late maternal inflammation disrupts the mother/pup interaction, resulting in long-lasting effects on pup behavior and alterations in biological pathways, thereby programming prepubertal behavior and the pups' inflammatory responses after bacterial endotoxin treatment. Female rats received 100 μg/kg lipopolysaccharide (LPS) or .9% saline solution on gestation day 18. Reproductive performance was observed at birth. On lactation days (LD) 5 and LD 6, respectively, maternal behavior and maternal aggressive behavior were assessed. In pups, maternal odor preference on LD 7, open field behavior on LD 21, and serum tumor necrosis factor α (TNF-α) levels after LPS challenge on LD 21 were investigated. The results showed that prenatal LPS exposure improved maternal care and reduced maternal aggressive behavior but did not alter maternal reproductive performance. Male offspring exhibited increased body weights at birth and reduced maternal odor preference. Lipopolysaccharide challenge increased the duration of immobility in the open field and induced a slight increase in serum TNF-α levels. Prenatal exposure to LPS during late pregnancy improved maternal care, reduced maternal olfactory preference, and induced TNF-α hyporesponsiveness to a single dose of LPS in pups.

Highlights

Intrauterine infection and inflammation are known risk factors for brain injuries in neonates
We previously found that prenatal LPS treatment on GD 9.5 impaired maternal odor preference and cat odor aversion, both of which were related to decreased dopamine levels in the olfactory bulb (Kirsten et al, 2011)
The present findings showed that prenatal LPS exposure (100 μg/kg on GD 18) improved maternal care and reduced maternal aggressive behavior but did not alter maternal reproductive performance

Summary

Introduction

Intrauterine infection and inflammation are known risk factors for brain injuries in neonates. Intrauterine inflammation leads to a dysregulation of the developing brain, known as fetal inflammatory response syndrome (de Moura, Lisboa, & Passos, 2008), regardless of the gestational age (Burd, Balakrishnan, & Kannan, 2012). Previous studies from our group showed that prenatal LPS treatment (100 μg/ kg, intraperitoneally, on gestational day [GD] 9.5) in male offspring reduced social behavior in infancy and adulthood, decreased dopamine and metabolite levels in the striatum and decreased general activity in the open field after an LPS challenge without signs of permanent neuroinflammation (Kirsten et al, 2011; Kirsten, Taricano, Florio, Palermo-Neto, & Bernardi, 2010b; Kirsten, Taricano, Maiorka, Palermo-Neto, & Bernardi, 2010a). Prenatal LPS exposure on GD 14 to GD 20 decreased adult neurogenesis in the dentate gyrus, caused persistent microglial activation, downregulated transforming growth factor β1 in the hippocampus, and impaired performance in the novel object recognition test (Graciarena, Depino, & Pitossi, 2010)

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Results

Conclusion