PMID- 26385575 OWN - NLM STAT- MEDLINE DCOM- 20160914 LR - 20200325 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 65 DP - 2016 Feb 4 TI - Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia. PG - 118-26 LID - S0278-5846(15)30042-7 [pii] LID - 10.1016/j.pnpbp.2015.09.006 [doi] AB - Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. CI - Crown Copyright (c) 2015. Published by Elsevier Inc. All rights reserved. FAU - Duchatel, Ryan J AU - Duchatel RJ AD - Preclinical Neurobiology Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia. Electronic address: ryan.duchatel@uon.edu.au. FAU - Jobling, Phillip AU - Jobling P AD - Preclinical Neurobiology Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address: Phillip.Jobling@newcastle.edu.au. FAU - Graham, Brett A AU - Graham BA AD - Preclinical Neurobiology Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address: Brett.Graham@newcastle.edu.au. FAU - Harms, Lauren R AU - Harms LR AD - School of Psychology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia. Electronic address: Lauren.Harms@newcastle.edu.au. FAU - Michie, Patricia T AU - Michie PT AD - School of Psychology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia. Electronic address: Pat.Michie@newcastle.edu.au. FAU - Hodgson, Deborah M AU - Hodgson DM AD - School of Psychology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia. Electronic address: Deborah.Hodgson@newcastle.edu.au. FAU - Tooney, Paul A AU - Tooney PA AD - Preclinical Neurobiology Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia. Electronic address: paul.tooney@newcastle.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150915 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 0 (Antigens, Nuclear) RN - 0 (Nerve Tissue Proteins) RN - 0 (Rbfox3 protein, rat) RN - 51110-01-1 (Somatostatin) RN - O84C90HH2L (Poly I-C) SB - IM MH - Animals MH - Antigens, Nuclear/metabolism MH - Brain/growth & development/immunology/*pathology MH - Cell Count MH - Disease Models, Animal MH - Female MH - Fluorescent Antibody Technique MH - *Immune System Diseases MH - Male MH - Nerve Tissue Proteins/metabolism MH - Neurons/immunology/*pathology MH - Poly I-C MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats, Wistar MH - Schizophrenia/immunology/*pathology MH - Sex Characteristics MH - Somatostatin/metabolism MH - White Matter/immunology/*pathology OTO - NOTNLM OT - Interstitial white matter neuron OT - Maternal immune activation OT - Polyinosinic:polycytidylic acid OT - Prenatal immune challenge OT - Schizophrenia OT - Somatostatin EDAT- 2015/09/20 06:00 MHDA- 2016/09/15 06:00 CRDT- 2015/09/20 06:00 PHST- 2015/07/17 00:00 [received] PHST- 2015/09/04 00:00 [revised] PHST- 2015/09/11 00:00 [accepted] PHST- 2015/09/20 06:00 [entrez] PHST- 2015/09/20 06:00 [pubmed] PHST- 2016/09/15 06:00 [medline] AID - S0278-5846(15)30042-7 [pii] AID - 10.1016/j.pnpbp.2015.09.006 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:118-26. doi: 10.1016/j.pnpbp.2015.09.006. Epub 2015 Sep 15.