title: A stereological comparison of GAD67 and reelin expression in the hippocampal stratum oriens of offspring from two mouse models of maternal inflammation during pregnancy.
abstract: Epidemiological evidence suggests that maternal infection during pregnancy may be a risk factor for schizophrenia and autism. Altered expression of glutamic acid decarboxylase (GAD67) and reelin in the hippocampus has been reported in post-mortem studies of people with schizophrenia or autism. We used two mouse models of maternal inflammation, featuring either the viral RNA mimic, poly (I:C), or the bacterial endotoxin, lipopolysaccharide (LPS), to compare effects of maternal inflammation on GAD67 and reelin expression in the hippocampal stratum oriens of juvenile mice. Pregnant Swiss-Webster mice were treated with poly (I:C) or LPS on gestational day 9. At postnatal days (PD) 14 and 28, brains from male and female offspring were processed immunohistochemically, and NeuN-, GAD67- and reelin-positive cells estimated using unbiased stereological cell counting methods. In offspring at PD14, GAD67 and reelin expression were unaffected by prenatal poly (I:C) or prenatal LPS treatment, although prenatal LPS mice showed increased neuronal (NeuN) density at this age. However, at PD28, mice prenatally treated with poly (I:C) displayed a decreased number of reelin-positive cells in dorsal stratum oriens. Interestingly, at PD28, we also found increased GAD67 expression in the ventral stratum oriens in male mice prenatally treated with LPS, and in female mice prenatally treated with poly (I:C). Our findings describe sex-, age-, and immunogen-specific alterations in regional hippocampal GAD67 and reelin expression as a result of early maternal inflammation. These neurodevelopmental changes could have significant effects on GABAergic neurotransmission and synaptic plasticity.
authors.affiliation: Department of Psychiatry, McGill University, Douglas Mental Health University Institute, 6875 La Salle Blvd, Verdun H4H 1R3, Quebec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Harvey
authors.forename: Patricia
authors.initials: P
authors.lastname: Boksa
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002452:Cell Count; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1