Article: Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: Evidence from MRI in a mouse model

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TitlePrenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: Evidence from MRI in a mouse model
AuthorsLi, Q2
Cheung, C2
Wei, R2
Hui, ES2
Feldon, J1
Meyer, U1
Chung, S2
Chua, SE2
Sham, PC2
Wu, EX2
McAlonan, GM2
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
CitationPlos One, 2009, v. 4 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0006354
AbstractObjectives: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method: We used an established mouse model of maternal immune activation (MIA) by the viral mimic Polyl:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results: Polyl:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. © 2009 Li et al.
ISSN1932-6203
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
DOIhttp://dx.doi.org/10.1371/journal.pone.0006354
ISI Accession Number IDWOS:000268318900006
PubMed Central IDPMC2710518
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, Q
dc.contributor.authorCheung, C
dc.contributor.authorWei, R
dc.contributor.authorHui, ES
dc.contributor.authorFeldon, J
dc.contributor.authorMeyer, U
dc.contributor.authorChung, S
dc.contributor.authorChua, SE
dc.contributor.authorSham, PC
dc.contributor.authorWu, EX
dc.contributor.authorMcAlonan, GM
dc.date.accessioned2010-10-31T11:24:55Z
dc.date.available2010-10-31T11:24:55Z
dc.date.issued2009
dc.description.abstractObjectives: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method: We used an established mouse model of maternal immune activation (MIA) by the viral mimic Polyl:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results: Polyl:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. © 2009 Li et al.
dc.description.naturepublished_or_final_version
dc.identifier.citationPlos One, 2009, v. 4 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0006354
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0006354
dc.identifier.hkuros174144
dc.identifier.isiWOS:000268318900006
dc.identifier.issn1932-6203
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
dc.identifier.issue7
dc.identifier.openurl
dc.identifier.pmcidPMC2710518
dc.identifier.pmid19629183
dc.identifier.scopuseid_2-s2.0-67749147581
dc.identifier.spagee6354
dc.identifier.urihttp://hdl.handle.net/10722/125328
dc.identifier.volume4
dc.languageeng
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
dc.publisher.placeUnited States
dc.relation.ispartofPLoS ONE
dc.relation.referencesReferences in Scopus
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subject.meshBehavior, Animal
dc.subject.meshBrain - pathology
dc.subject.meshDisease Models, Animal
dc.subject.meshMagnetic Resonance Imaging - methods
dc.subject.meshMaternal Exposure
dc.titlePrenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: Evidence from MRI in a mouse model
dc.typeArticle
Author Affiliations
  1. Eidgenossische Technische Hochschule Zurich
  2. The University of Hong Kong