title: Developmental disruption of perineuronal nets in the medial prefrontal cortex after maternal immune activation.
abstract: Maternal infection during pregnancy increases the risk of offspring developing schizophrenia later in life. Similarly, animal models of maternal immune activation (MIA) induce behavioural and anatomical disturbances consistent with a schizophrenia-like phenotype in offspring. Notably, cognitive impairments in tasks dependent on the prefrontal cortex (PFC) are observed in humans with schizophrenia and in offspring after MIA during pregnancy. Recent studies of post-mortem tissue from individuals with schizophrenia revealed deficits in extracellular matrix structures called perineuronal nets (PNNs), particularly in PFC. Given these findings, we examined PNNs over the course of development in a well-characterized rat model of MIA using polyinosinic-polycytidylic acid (polyI:C). We found selective reductions of PNNs in the PFC of polyI:C offspring which did not manifest until early adulthood. These deficits were not associated with changes in parvalbumin cell density, but a decrease in the percentage of parvalbumin cells surrounded by a PNN. Developmental expression of PNNs was also significantly altered in the amygdala of polyI:C offspring. Our results indicate MIA causes region specific developmental abnormalities in PNNs in the PFC of offspring. These findings confirm the polyI:C model replicates neuropathological alterations associated with schizophrenia and may identify novel mechanisms for cognitive and emotional dysfunction in the disorder.
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, T6G 2E1, AB, Canada.|Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, T6G 2B7, AB, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Paylor
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, S7N 5E5, SK, Canada.
authors.forename: Brittney R
authors.initials: BR
authors.lastname: Lins
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, S7N 5E5, SK, Canada.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Greba
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moen
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, T6G 2E1, AB, Canada.
authors.forename: Reiner Silveira
authors.initials: RS
authors.lastname: de Moraes
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, S7N 5E5, SK, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Howland
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, T6G 2E1, AB, Canada.|Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, T6G 2B7, AB, Canada.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Winship
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D007109:Immunity / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000276:immunology*; D011247:Pregnancy; D020318:Rats, Long-Evans
chemical_list: D015415:Biomarkers; D010320:Parvalbumins; D011070:Poly I-C