title: Gender-dependent effects of maternal immune activation on the behavior of mouse offspring.
abstract: Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
authors.forename: Ingrid C Y
authors.initials: IC
authors.lastname: Xuan
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Hampson
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002659:Child Development Disorders, Pervasive / Q000276:immunology* / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009035:Mothers; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology*; D012727:Sex Characteristics; D012919:Social Behavior
chemical_list: D008070:Lipopolysaccharides; D011070:Poly I-C
references.citation: Pediatrics. 2012 Dec;130(6):e1447-54
references.pmid: 23147969
references.citation: Brain Behav Immun. 2013 Jul;31:54-68
references.pmid: 22841693
references.citation: Behav Brain Res. 2012 Jun 15;232(1):30-6
references.pmid: 22487249
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Ann N Y Acad Sci. 2004 Jun;1018:281-7
references.pmid: 15240379
references.citation: J Neurosci Methods. 2005 Apr 30;143(2):169-77
references.pmid: 15814150
references.citation: Mol Cell Neurosci. 2013 Mar;53:52-62
references.pmid: 23064447
references.citation: Mol Cell Neurosci. 2011 Mar;46(3):563-72
references.pmid: 21215802
references.citation: Ann Neurol. 2005 Jan;57(1):67-81
references.pmid: 15546155
references.citation: Res Dev Disabil. 2011 Nov-Dec;32(6):2346-51
references.pmid: 21824745
references.citation: Annu Rev Public Health. 2007;28:235-58
references.pmid: 17367287
references.citation: Dev Neurobiol. 2012 Oct;72(10):1335-48
references.pmid: 22730147
references.citation: J Neuroimmunol. 2011 Mar;232(1-2):196-9
references.pmid: 21095018
references.citation: Trends Mol Med. 2011 Jul;17(7):389-94
references.pmid: 21482187
references.citation: J Autism Dev Disord. 2010 Dec;40(12):1423-30
references.pmid: 20414802
references.citation: Biol Psychiatry. 2009 Dec 1;66(11):1038-46
references.pmid: 19726031
references.citation: J Autism Dev Disord. 2012 Jul;42(7):1304-13
references.pmid: 21947663
references.citation: Neurotherapeutics. 2010 Jul;7(3):283-92
references.pmid: 20643381
references.citation: Res Dev Disabil. 2013 Jan;34(1):413-22
references.pmid: 23023300
references.citation: Psychopharmacology (Berl). 2009 Jun;204(2):361-73
references.pmid: 19189082
references.citation: Nat Rev Neurosci. 2010 Jul;11(7):490-502
references.pmid: 20559336
references.citation: Curr Opin Neurol. 2013 Apr;26(2):146-53
references.pmid: 23406909
references.citation: J Neurosci. 2013 May 1;33(18):7654-66
references.pmid: 23637159
references.citation: Mol Psychiatry. 2012 Jan;17(1):62-70
references.pmid: 21079609
references.citation: J Autism Dev Disord. 2006 Apr;36(3):429-35
references.pmid: 16568356
references.citation: Mol Psychiatry. 2014 Feb;19(2):259-64
references.pmid: 23337946
references.citation: Psychol Med. 2011 Mar;41(3):619-27
references.pmid: 21272389
references.citation: Brain Behav Immun. 2012 May;26(4):607-16
references.pmid: 22310922
references.citation: Trends Immunol. 2002 Mar;23(3):135-9
references.pmid: 11864841
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2012 Jan;159B(1):5-12
references.pmid: 22095612
references.citation: Curr Opin Pediatr. 2011 Dec;23(6):609-15
references.pmid: 21970828
references.citation: Behav Brain Res. 2009 Dec 7;204(2):313-21
references.pmid: 19136031
references.citation: Arch Gen Psychiatry. 2011 Nov;68(11):1095-102
references.pmid: 21727249
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12776-81
references.pmid: 22802640
references.citation: Horm Behav. 2012 Aug;62(3):228-36
references.pmid: 22516179
references.citation: J Neurosci Res. 2012 Oct;90(10):1903-12
references.pmid: 22714803
references.citation: Res Dev Disabil. 2007 Jul-Sep;28(4):341-52
references.pmid: 16765022
references.citation: Behav Brain Res. 2010 Jul 29;211(1):77-82
references.pmid: 20226214
references.citation: Annu Rev Clin Psychol. 2008;4:275-303
references.pmid: 18370618
references.citation: Am J Psychiatry. 2011 Sep;168(9):904-12
references.pmid: 21558103
references.citation: Science. 2013 Aug 16;341(6147):789-92
references.pmid: 23907535
references.citation: Transl Psychiatry. 2013 Mar 12;3:e240
references.pmid: 23481627
references.citation: Nat Rev Genet. 2008 May;9(5):341-55
references.pmid: 18414403
references.citation: Mol Psychiatry. 2006 Jan;11(1):47-55
references.pmid: 16189509
references.citation: J Autism Dev Disord. 2012 Dec;42(12):2585-96
references.pmid: 22453928
references.citation: J Neurochem. 2013 Mar;124(6):832-43
references.pmid: 23311691
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5795-800
references.pmid: 21436042
references.citation: J Neurosci Res. 2013 Mar;91(3):462-71
references.pmid: 23239187
references.citation: Biol Psychiatry. 2010 Aug 15;68(4):368-76
references.pmid: 20674603