Cited by 603Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsStress Responses and Cortisol

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Effects of prenatal infection on brain development and behavior: A review of findings from animal models

Boksa, Patricia·2010·Brain, Behavior, and Immunity

DOI 10.1016/j.bbi.2010.03.005

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Abstract

Epidemiological studies with human populations indicate associations between maternal infection during pregnancy and increased risk in offspring for central nervous system (CNS) disorders including schizophrenia, autism and cerebral palsy. Since 2000, a large number of studies have used rodent models of systemic prenatal infection or prenatal immune activation to characterize changes in brain function and behavior caused by the prenatal insult. This review provides a comprehensive summary of these findings, and examines consistencies and trends across studies in an effort to provide a perspective on our current state of understanding from this body of work. Results from these animal modeling studies clearly indicate that prenatal immune activation can cause both acute and lasting changes in behavior and CNS structure and function in offspring. Across laboratories, studies vary with respect to the type, dose and timing of immunogen administration during gestation, species used, postnatal age examined and specific outcome measure quantified. This makes comparison across studies and assessment of replicability difficult. With regard to mechanisms, evidence for roles for several acute mediators of effects of prenatal immune activation has emerged, including circulating interleukin-6, increased placental cytokines and oxidative stress in the fetal brain. However, information required to describe the complete mechanistic pathway responsible for acute effects of prenatal immune activation on fetal brain is lacking, and no studies have yet addressed the issue of how acute prenatal exposure to an immunogen is transduced into a long-term CNS change in the postnatal animal. Directions for further research are discussed.

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Suzuki, E., Ichihara, K., & JOHNSON, A. M. (2007) · Clinical Pediatrics · doi:10.1177/0009922806289588 · Cited by 19
Transplacental Effects of Endotoxemia on Fetal Mouse Brain, Bone, and Placental Tissue
Haesaert, B., & Ornoy, A. (1986) · Pediatric Pathology · doi:10.3109/15513818609041199 · Cited by 16
Prenatal inflammatory effects on nigrostriatal development in organotypic cultures
Snyder‐Keller, A., & Stark, P. F. (2008) · Brain Research · doi:10.1016/j.brainres.2008.07.106 · Cited by 13
Lipopolysaccharide (LPS) Up-Regulates the Expression of Haem Oxygenase-1 in Mouse Placenta
Zhang, C., Li, X.-Y., Zhao, L., Wang, H., & Xu, D.-X. (2007) · Placenta · doi:10.1016/j.placenta.2007.04.003 · Cited by 13
Endotoxin exposure in utero increases ethanol consumption in adult male offspring
Liu, X., Lee, J. G., Yee, S. K., Bresee, C. J., Poland, R. E., & Pechnick, R. N. (2003) · Neuroreport · doi:10.1097/00001756-200401190-00039 · Cited by 12
Endotoxin treatment of pregnant rats affects sexual behavior of the male offspring
Wijkstra, S., Valkhof, N., Koolhaas, J. M., & Schuiling, G. A. (1991) · Physiology & Behavior · doi:10.1016/0031-9384(91)90294-x · Cited by 6

Flagged first, then by citations

2 of the 185 references couldn’t be matched to a known paper.

Sorted by citations

The role of inflammation in perinatal brain injury
Hagberg, H., Mallard, C. E., Ferriero, D. M., Vannucci, S. J., Levison, S. W., Vexler, Z. S., & Gressèns, P. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.13 · Cited by 852
Animal models of schizophrenia
Jones, C., Watson, D., & Fone, K. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01386.x · Cited by 771
Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders
Krakowiak, P., Walker, C. K., Bremer, A. A., Baker, A. S., Ozonoff, S., Hansen, R. L., & Hertz-Picciotto, I. (2012) · PEDIATRICS · doi:10.1542/peds.2011-2583 · Cited by 675
Early Adverse Experiences and the Developing Brain
Bick, J., & Nelson, C. A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.252 · Cited by 559
The Role of the Immune System in Autism Spectrum Disorder
Meltzer, A., & Van de Water, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.158 · Cited by 533

See all 603

Authors: Boksa, P.
Affiliations: Douglas Mental Health University Institute (CA)
Corresponding author: Boksa, Patricia
ORCID: Boksa, Patricia
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 2010-08
Volume: 24
Issue: 6
Pages: 881-897
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2010.03.005
OpenAlex: W2007305673
Cited by: 603
References: 185
Citations by year: 2026: 10 · 2025: 16 · 2024: 22 · 2023: 24 · 2022: 43 · 2021: 33 · 2020: 38 · 2019: 34 · 2018: 48 · 2017: 30 · 2016: 49 · 2015: 48 · 2014: 49 · 2013: 52 · 2012: 48
FWCI: 3.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: prenatal infection, prenatal immune activation, maternal infection, rodent models, brain development, offspring behavior, schizophrenia, autism spectrum disorder, cerebral palsy, interleukin-6, placental cytokines, oxidative stress, fetal brain, central nervous system disorders
MeSH terms: Animals, Behavior, Animal, Brain, Brain Chemistry, Disease Models, Animal, Female, Fetus, Infections, Pregnancy, Prenatal Exposure Delayed Effects, Mice, Rats

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Effects of prenatal infection on brain development and behavior: A review of findings from animal models

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