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Conference Paper: The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia

TitleThe timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia
Authors
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/schres
Citation
The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 10-14 April 2010. In Schizophrenia Research, 2010, v. 117 n. 2-3, p. 392, poster 213 How to Cite?
AbstractBACKGROUND: Imaging and neuropathological studies point to the onset of pathology in neurodevelopmental disorders such as schizophrenia early in fetal life. White matter connections appear to be disrupted, leading to altered functional connectivity during higherorder cognitive processing. We have previously reported diffusion tensor imaging (DTI) evidence of microstructural pathology in our clinical studies of schizophrenia at first-episode and prior to drug treatment, but direct evidence for a fetal trigger of these brain structural differences is sparse. Epidemiological studies implicate maternal inflammation during prenatal life as an environmental risk factor for schizophrenia in the offspring. In this study we tested the hypothesis that maternal immune activation causes post-natal white matter microstructural anomalies in offspring relevant to schizophrenia or autism. We examined the effects of maternal inflammation in early and late gestation on white matter microstructure in the offspring using advanced in-vivo MR-DTI. METHODS: We used an mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. A novel application of automated voxel-based morphometry (VBM) of in-vivo MRI data mapped fractional anisotropy (FA, directional diffusion ofwater) acrosswhitematter pathways of adult offspring. Region-of-interest manual tracing was used to confirm FA changes in selected white matter tracts. In addition we conducted a preliminary immunohistochemical exploration of the oligodendrocyte marker CNPase to determine whether myelination processes might contribute to any changes in FA observed. RESULTS: FA was lower in MIA exposed offspring throughout frontostriatal-limbic circuits and in the corpus callosum. Regions with lower FA were more extensive in the early exposed group. In both groups there were regions with increased FA but again, these were more extensive in the early exposed group. Preliminary immunohistochemical evidence revealed reduction in the oligodendrocyte marker CNPase in mice exposed to MIA, consistent with a white matter structural insult affecting myelination. DISCUSSION: The present results provide direct experimental evidence that prenatal inflammation causes white matter microstructural abnormalities analogous to those found in schizophrenia. Maternal inflammation earlier in gestation precipitates more extensive changes in offspring, suggesting that the fetus is more vulnerable to environmental insults associated with schizophrenia early in development.
DescriptionThis journal issues are conference proceedings of SIRS 2010
Persistent Identifierhttp://hdl.handle.net/10722/126812
ISSN
2015 Impact Factor: 4.453
2015 SCImago Journal Rankings: 2.304
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMcAlonan, GMen_HK
dc.contributor.authorCheung, Cen_HK
dc.contributor.authorLi, Qen_HK
dc.contributor.authorCheung, Ven_HK
dc.contributor.authorHui, ESKen_HK
dc.contributor.authorWei, Ren_HK
dc.contributor.authorWong, Pen_HK
dc.contributor.authorChua, SEen_HK
dc.contributor.authorWu, EXen_HK
dc.date.accessioned2010-10-31T12:49:58Z-
dc.date.available2010-10-31T12:49:58Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 10-14 April 2010. In Schizophrenia Research, 2010, v. 117 n. 2-3, p. 392, poster 213en_HK
dc.identifier.issn0920-9964-
dc.identifier.urihttp://hdl.handle.net/10722/126812-
dc.descriptionThis journal issues are conference proceedings of SIRS 2010-
dc.description.abstractBACKGROUND: Imaging and neuropathological studies point to the onset of pathology in neurodevelopmental disorders such as schizophrenia early in fetal life. White matter connections appear to be disrupted, leading to altered functional connectivity during higherorder cognitive processing. We have previously reported diffusion tensor imaging (DTI) evidence of microstructural pathology in our clinical studies of schizophrenia at first-episode and prior to drug treatment, but direct evidence for a fetal trigger of these brain structural differences is sparse. Epidemiological studies implicate maternal inflammation during prenatal life as an environmental risk factor for schizophrenia in the offspring. In this study we tested the hypothesis that maternal immune activation causes post-natal white matter microstructural anomalies in offspring relevant to schizophrenia or autism. We examined the effects of maternal inflammation in early and late gestation on white matter microstructure in the offspring using advanced in-vivo MR-DTI. METHODS: We used an mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. A novel application of automated voxel-based morphometry (VBM) of in-vivo MRI data mapped fractional anisotropy (FA, directional diffusion ofwater) acrosswhitematter pathways of adult offspring. Region-of-interest manual tracing was used to confirm FA changes in selected white matter tracts. In addition we conducted a preliminary immunohistochemical exploration of the oligodendrocyte marker CNPase to determine whether myelination processes might contribute to any changes in FA observed. RESULTS: FA was lower in MIA exposed offspring throughout frontostriatal-limbic circuits and in the corpus callosum. Regions with lower FA were more extensive in the early exposed group. In both groups there were regions with increased FA but again, these were more extensive in the early exposed group. Preliminary immunohistochemical evidence revealed reduction in the oligodendrocyte marker CNPase in mice exposed to MIA, consistent with a white matter structural insult affecting myelination. DISCUSSION: The present results provide direct experimental evidence that prenatal inflammation causes white matter microstructural abnormalities analogous to those found in schizophrenia. Maternal inflammation earlier in gestation precipitates more extensive changes in offspring, suggesting that the fetus is more vulnerable to environmental insults associated with schizophrenia early in development.-
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/schres-
dc.relation.ispartofSchizophrenia Research-
dc.titleThe timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophreniaen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0920-9964&volume=117&issue=2-3&spage=392, poster 213&epage=&date=2010&atitle=The+timing+of+prenatal+immune+challenge+determines+the+extent+of+white+matter+microstructural+anomalies+relevant+to+schizophrenia-
dc.identifier.emailMcAlonan, GM: mcalonan@hkucc.hku.hken_HK
dc.identifier.emailCheung, C: charlton@hkucc.hku.hken_HK
dc.identifier.emailLi, Q: ciqi@hkucc.hku.hken_HK
dc.identifier.emailCheung, V: cheungv@graduate.hku.hken_HK
dc.identifier.emailWei, R: weiranapply@hotmail.comen_HK
dc.identifier.emailChua, SE: sechua@hku.hken_HK
dc.identifier.emailWu, EX: ewu@eee.hku.hk-
dc.identifier.authorityMcAlonan, GM=rp00475en_HK
dc.identifier.authorityChua, SE=rp00438en_HK
dc.identifier.doi10.1016/j.schres.2010.02.708-
dc.identifier.hkuros172316en_HK
dc.identifier.volume117-
dc.identifier.issue2-3-
dc.identifier.spage392, poster 213-
dc.identifier.epage392, poster 213-
dc.identifier.isiWOS:000276936801077-
dc.description.otherThe 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 10-14 April 2010. In Schizophrenia Research, 2010, v. 117 n. 2-3, p. 392, poster 213-

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