title: Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure.
abstract: A significant feature of the cortical neuropathology of schizophrenia is a disturbance in the biogenesis of short non-coding microRNA (miRNA) that regulate translation and stability of mRNA. While the biological origin of this phenomenon has not been defined, it is plausible that it relates to major environmental risk factors associated with the disorder such as exposure to maternal immune activation (MIA) and adolescent cannabis use. To explore this hypothesis, we administered the viral mimic poly I:C to pregnant rats and further exposed some of their maturing offsprings to daily injections of the synthetic cannabinoid HU210 for 14 days starting on postnatal day 35. Whole-genome miRNA expression analysis was then performed on the left and right hemispheres of the entorhinal cortex (EC), a region strongly associated with schizophrenia. Animals exposed to either treatment alone or in combination exhibited significant differences in the expression of miRNA in the left hemisphere, whereas the right hemisphere was less responsive. Hemisphere-associated differences in miRNA expression were greatest in the combined treatment and highly over-represented in a single imprinted locus on chromosome 6q32. This observation was significant as the syntenic 14q32 locus in humans encodes a large proportion of miRNAs differentially expressed in peripheral blood lymphocytes from patients with schizophrenia, suggesting that interaction of early and late environmental insults may affect miRNA expression, in a manner that is relevant to schizophrenia.
authors.affiliation: 1] School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia [2] Schizophrenia Research Institute, Sydney, NSW, Australia [3] Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Hollins
authors.affiliation: 1] School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia [2] Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Zavitsanou
authors.affiliation: 1] School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia [2] The Centre for Translational Neuroscience and Mental Health, Callaghan, NSW, Australia.
authors.forename: F R
authors.initials: FR
authors.lastname: Walker
authors.affiliation: 1] School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia [2] Schizophrenia Research Institute, Sydney, NSW, Australia [3] Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cairns
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D018728:Entorhinal Cortex; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018392:Genomic Imprinting / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D007453:Iodide Peroxidase / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D008297:Male; D018811:Maternal Exposure; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002186:Cannabinoids; C512923:Dlk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase