title: Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Duchatel
authors.affiliation: 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.
authors.forename: Phillip
authors.initials: P
authors.lastname: Jobling
authors.affiliation: 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.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Graham
authors.affiliation: 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.
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Harms
authors.affiliation: 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.
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Michie
authors.affiliation: 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.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Hodgson
authors.affiliation: 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.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tooney
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000276:immunology / Q000473:pathology*; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007154:Immune System Diseases; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000473:pathology*; D011070:Poly I-C; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D012559:Schizophrenia / Q000276:immunology / Q000473:pathology*; D012727:Sex Characteristics; D013004:Somatostatin / Q000378:metabolism; D066127:White Matter / Q000276:immunology / Q000473:pathology*
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D013004:Somatostatin; D011070:Poly I-C
keywords: Interstitial white matter neuron; Maternal immune activation; Polyinosinic:polycytidylic acid; Prenatal immune challenge; Schizophrenia; Somatostatin