title: The different effects of LPS and poly I:C prenatal immune challenges on the behavior, development and inflammatory responses in pregnant mice and their offspring.
abstract: In recent years, in vivo animal models of prenatal infection have been developed in an attempt to recreate behavioral and neuropathological features associated to a number of neurological and neuropsychiatric disorders. However, these models are still in their emerging phase and a better understanding of how these types of infections relate to adult-onset of brain-related disorders is needed. Here, we undertook an extensive behavioral characterization of both pregnant females and their pups following late gestational exposure (from gestational days (GD) 15-17) to either lipopolysaccharide (LPS; 120μg/kg i.p.) or polyinosinic:polycytidylic acid (poly I:C; 5mg/kg i.v.). We observed that both LPS and poly I:C treatments produced anxiety-like behaviors in treated pregnant females, although to a lesser extent with LPS. LPS injections, but not poly I:C, led to reduced food intake and consequently decreased weight gain in pregnant dams. In pups, poly I:C treatments triggered a delay in growth and sensorimotor development, as evaluated by righting, geotaxis and grasping reflexes. At the cellular level, both toxins induced an initial inflammatory response while only LPS reduced the expression of brain cell markers in foetuses (GFAP and NeuN), which was no longer observable at postnatal day (PnD) 10. Higher levels of IL-2, IL-5 and IL-6 in plasma and an upregulation of the metabotropic receptor 5 (mGluR5) in foetal brains of 10-day-old offspring prenatally exposed to poly I:C was also observed. Interestingly, the increased mGluR5 expression correlated with impairments of the righting reflex. This study is the first to directly compare reflex development following LPS and poly I:C prenatal immune challenges in mice and sheds light onto the different patterns of behavior and pathology in dams and their offspring.
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
authors.forename: Dany
authors.initials: D
authors.lastname: Arsenault
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cisbani
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
authors.forename: Louis-Simon
authors.initials: LS
authors.lastname: Rousseau
authors.affiliation: Centre de Recherche du CHU de Québec (CHUQ), Axe Neurosciences, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada; Département de Psychiatrie et Neurosciences, Université Laval, Québec, QC G1K 7P4, Canada. Electronic address: Francesca.Cicchetti@crchul.ulaval.ca.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cicchetti
mesh_terms: D000818:Animals; D001007:Anxiety / Q000276:immunology*; D001921:Brain / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D011070:Poly I-C
keywords: Behavior; Cytokines; Development; Immune response; Inflammation; mGluR5