title: Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure.
abstract: Maternal immune activation (MIA) and adolescent cannabinoid exposure (ACE) have both been identified as major environmental risk factors for schizophrenia. We examined the effects of these two risk factors alone, and in combination, on gene expression during late adolescence. Pregnant rats were exposed to the viral infection mimic polyriboinosinic-polyribocytidylic acid (poly I:C) on gestational day (GD) 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14days starting on postnatal day (PND) 35. Gene expression was examined in the left entorhinal cortex (EC) using mRNA microarrays. We found prenatal treatment with poly I:C alone, or HU210 alone, produced relatively minor changes in gene expression. However, following combined treatments, offspring displayed significant changes in transcription. This dramatic and persistent alteration of transcriptional networks enriched with genes involved in neurotransmission, cellular signalling and schizophrenia, was associated with a corresponding perturbation in the expression of small non-coding microRNA (miRNA). These results suggest that a combination of environmental exposures during development leads to significant genomic remodeling that disrupts maturation of the EC and its associated circuitry with important implications as the potential antecedents of memory and learning deficits in schizophrenia and other neuropsychiatric disorders.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hollins
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Zavitsanou
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia.
authors.forename: Frederick Rohan
authors.initials: FR
authors.lastname: Walker
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Schizophrenia Research Institute, Sydney, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia. Electronic address: murray.cairns@newcastle.edu.au.
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Cairns
mesh_terms: D000367:Age Factors; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014777:Virus Diseases / Q000276:immunology
chemical_list: D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol; D011070:Poly I-C; C062018:HU 211
keywords: Brain; Cannabinoid; Entorhinal cortex; Gene expression; Maternal infection; Schizophrenia