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Maternal immune activation induced by lipopolysaccharide triggers immune response in pregnant mother and fetus, and induces behavioral impairment in adult rats.

Abstract
Evidence suggest that prenatal immune system disturbance contributes largely to the pathophysiology of neuropsychiatric disorders. We investigated if maternal immune activation (MIA) could induce inflammatory alterations in fetal brain and pregnant rats. Adult rats subjected to MIA also were investigated to evaluate if ketamine potentiates the effects of infection. On gestational day 15, Wistar pregnant rats received lipopolysaccharide (LPS) to induce MIA. After 6, 12 and 24 h, fetus brain, placenta, and amniotic fluid were collected to evaluate early effects of LPS. MIA increased oxidative stress and expression of metalloproteinase in the amniotic fluid and fetal brain. The blood brain barrier (BBB) integrity in the hippocampus and cortex as well integrity of placental barrier (PB) in the placenta and fetus brain were dysregulated after LPS induction. We observed elevated pro- and anti-inflammatory cytokines after LPS in fetal brain. Other group of rats from postnatal day (PND) 54 after LPS received injection of ketamine at the doses of 5, 15, and 25 mg/kg. On PND 60 rats were subjected to the memories tests, spontaneous locomotor activity, and pre-pulse inhibition test (PPI). Rats that receive MIA plus ketamine had memory impairment and a deficit in the PPI. Neurotrophins were increased in the hippocampus and reduced in the prefrontal cortex in the LPS plus ketamine group. MIA induced oxidative stress and inflammatory changes that could be, at least in part, related to the dysfunction in the BBB and PB permeability of pregnant rats and offspring. Besides, this also generates behavioral deficits in the rat adulthood's that are potentiated by ketamine.
AuthorsLutiana Roque Simões, Gustavo Sangiogo, Michael Hikaru Tashiro, Jaqueline S Generoso, Cristiano Julio Faller, Diogo Dominguini, Gustavo Antunes Mastella, Giselli Scaini, Vijayasree Vayalanellore Giridharan, Monique Michels, Drielly Florentino, Fabricia Petronilho, Gislaine Zilli Réus, Felipe Dal-Pizzol, Alexandra I Zugno, Tatiana Barichello
JournalJournal of psychiatric research (J Psychiatr Res) Vol. 100 Pg. 71-83 (05 2018) ISSN: 1879-1379 [Electronic] England
PMID29494891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Ltd. All rights reserved.
Chemical References
  • Cytokines
  • Excitatory Amino Acid Antagonists
  • Lipopolysaccharides
  • Ketamine
Topics
  • Animals
  • Behavior, Animal (drug effects, physiology)
  • Blood-Brain Barrier (immunology)
  • Brain (drug effects, immunology, physiopathology)
  • Cytokines (metabolism)
  • Embryo, Mammalian
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Female
  • Inflammation (etiology, immunology)
  • Ketamine (pharmacology)
  • Lipopolysaccharides (pharmacology)
  • Male
  • Memory Disorders (chemically induced, immunology, physiopathology)
  • Placenta (immunology)
  • Pregnancy
  • Pregnancy Complications (chemically induced, immunology)
  • Prepulse Inhibition (drug effects, physiology)
  • Rats
  • Rats, Wistar

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