title: Peripubertal viral-like challenge and social isolation mediate overlapping but distinct effects on behaviour and brain interferon regulatory factor 7 expression in the adult Wistar rat.
abstract: A range of adverse, early life environmental influences such as viral infection and social deprivation are thought to increase risk of psychiatric illness later in life. Here, we used peripheral administration of the viral infection mimic polyriboinosinic-polyribocytidylic acid (polyI:C) to compare the consequences of peripubertal infection and isolation rearing. Isolation rearing induced deficits in sensorimotor gating and recognition memory while no changes in social interaction or spatial learning were observed. PolyI:C injection during the peripubertal period markedly increased expression of interferon-stimulated genes (Ifit2, Prkr, Mx2 and Irf7) in the hippocampal dentate gyrus demonstrating that peripheral administration of the viral mimic in the adolescent animal does have direct effects in the brain. Peripubertal infection mimicry induced a similar but later emerging behavioural deficit in prepulse inhibition implying the existence of a peripubertal window of opportunity for viral-mediated cytokine increases to impact brain development and function. PolyI:C treatment also impaired novel object recognition but did not alter spatial reference memory or social interaction. Combining the polyI:C challenge with social isolation did not exacerbate the behavioural deficits seen with isolation rearing alone. Using Irf7 as a marker, peripubertal viral infection mimicry, isolation rearing and a combination of both were all seen to produce a long-lasting molecular imprint on the interferon-associated signalling pathway in the principal neuron population of the hippocampal dentate gyrus. The data suggest that the sensitivity of brain structure and function to disruption by viral infection extends into the peripubertal period. Moreover, augmented interferon signalling in hippocampus may represent a common molecular imprint of environmental insults associated with neuropsychiatric illnesses like schizophrenia.
authors.affiliation: Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Lukasz
authors.forename: Niamh C
authors.initials: NC
authors.lastname: O'Sullivan
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Loscher
authors.forename: Mark
authors.initials: M
authors.lastname: Pickering
authors.forename: Ciaran M
authors.initials: CM
authors.lastname: Regan
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology*; D050839:Interferon Regulatory Factor-7 / Q000187:drug effects / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D008297:Male; D064547:Myxovirus Resistance Proteins; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D012741:Sexual Maturation / Q000502:physiology; D012934:Social Isolation; D014777:Virus Diseases / Q000378:metabolism*
chemical_list: D007369:Interferon Inducers; D050839:Interferon Regulatory Factor-7; C579066:Mx2 protein, rat; D064547:Myxovirus Resistance Proteins; D007372:Interferons; D019204:GTP-Binding Proteins; D011070:Poly I-C