title: Modulation of schizophrenia-related genes in the forebrain of adolescent and adult rats exposed to maternal immune activation.
abstract: Maternal immune activation (MIA) is an environmental risk factor for schizophrenia, and may contribute to other developmental disorders including autism and epilepsy. Activation of pro-inflammatory cytokine systems by injection of the synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C) mediates important neurochemical and behavioral corollaries of MIA, which have relevance to deficits observed in schizophrenia. We examined the consequences of MIA on forebrain expression of neuregulin-1 (NRG-1), brain-derived neurotrophic factor (BDNF) and their receptors, ErbB4 and trkB, respectively, genes associated with schizophrenia. On gestational day 14, pregnant rats were injected with Poly I:C or vehicle. Utilizing in situ hybridization, expression of NRG-1, ErbB4, BDNF, and trkB was examined in male rat offspring at postnatal day (P) 14, P30 and P60. ErbB4 mRNA expression was significantly increased at P30 in the anterior cingulate (AC Ctx), frontal, and parietal cortices, with increases in AC Ctx expression continuing through P60. ErbB4 expression was also elevated in the prefrontal cortex (PFC) at P14. In contrast, NRG-1 mRNA was decreased in the PFC at P60. Expression of BDNF mRNA was significantly upregulated in the PFC at P60 and decreased in the AC Ctx at P14. Expression of trkB was increased in two regions, the piriform cortex at P14 and the striatum at P60. These findings demonstrate developmentally and regionally selective alterations in the expression of schizophrenia-related genes as a consequence of MIA. Further study is needed to determine contributions of these effects to the development of alterations of relevance to neuropsychiatric diseases.
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hemmerle
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahlbrand
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, USA; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Bronson
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Kerstin H
authors.initials: KH
authors.lastname: Lundgren
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, USA; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; San Diego Veterans Affairs Healthcare System, San Diego, CA 92161, USA; Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, USA. Electronic address: kim.seroogy@uc.edu.
authors.forename: Kim B
authors.initials: KB
authors.lastname: Seroogy
mesh_terms: D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007369:Interferon Inducers / Q000633:toxicity; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D016548:Prosencephalon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007369:Interferon Inducers; D020890:Neuregulin-1; D012333:RNA, Messenger; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D020813:Receptor, trkB; D011070:Poly I-C
keywords: BDNF; ErbB4; Neuregulin-1; Poly I:C; trkB