Maternal immune activation induced by lipopolysaccharide triggers immune response in pregnant mother and fetus, and induces behavioral impairment in adult rats.
Autor: | Simões LR; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Sangiogo G; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Tashiro MH; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Generoso JS; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Faller CJ; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Dominguini D; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Mastella GA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Scaini G; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA., Giridharan VV; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA., Michels M; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Florentino D; Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina (UNISUL), Tubarão, SC, Brazil., Petronilho F; Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina (UNISUL), Tubarão, SC, Brazil., Réus GZ; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Dal-Pizzol F; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Zugno AI; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil., Barichello T; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA. Electronic address: Tatiana.Barichello@uth.tmc.edu. |
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Jazyk: | angličtina |
Zdroj: | Journal of psychiatric research [J Psychiatr Res] 2018 May; Vol. 100, pp. 71-83. Date of Electronic Publication: 2018 Feb 10. |
DOI: | 10.1016/j.jpsychires.2018.02.007 |
Abstrakt: | 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. (Copyright © 2018 Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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