Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat
Cristina A Ghiani,
Natalia S Mattan,
Hiroko Nobuta,
Jemily S Malvar,
Julie Boles,
Michael G Ross,
James A Waschek,
Ellen M Carpenter,
Robin S Fisher,
Jean de Vellis
Affiliations
Cristina A Ghiani
Intellectual and Developmental Disability Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Natalia S Mattan
Department of Neurobiology, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Hiroko Nobuta
Neuroscience Interdepartmental Program, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, U.S.A.
Jemily S Malvar
Department of Neurobiology, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Julie Boles
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90509, U.S.A.
Michael G Ross
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90509, U.S.A.
James A Waschek
Intellectual and Developmental Disability Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Ellen M Carpenter
Intellectual and Developmental Disability Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Robin S Fisher
Intellectual and Developmental Disability Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Jean de Vellis
Department of Neurobiology, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, U.S.A.
Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide)/kg to timed-pregnant rats at GD15 (gestational day 15) and GD16. Increased thickness of the CP (cortical plate) and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter), and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.
