title: Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation.
abstract: Exposure to prenatal infection and traumatizing experiences in peripubertal life are two environmental risk factors for developmental neuropsychiatric disorders. Modeling the cumulative neuronal impact of these factors in a translational animal model has led to the recent identification of pathological interactions between these environmental adversities in the development of adult brain dysfunctions. The present study explored the consequences of combined prenatal immune challenge and peripubertal stress on discrete cellular abnormalities in the γ-aminobutyric acid (GABA) system of the hippocampus. Pregnant mice were treated with the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic acid) or control solution, and offspring born to poly(I:C)-exposed or control mothers were then left undisturbed or subjected to unpredictable sub-chronic stress during peripubertal development. Stereological estimations of parvalbumin-expressing cells revealed a significant reduction of these GABAergic interneurons in the ventral dentate gyrus of adult offspring exposed to combined immune activation and stress. Single exposure to either environmental factor was insufficient to cause similar neuropathology. We further found that peripubertal stress exerted opposite effects on reelin-immunoreactive cells in the dorsal cornu ammonis (CA) region of the hippocampus, with stress increasing and decreasing reelin expression in control offspring and prenatally immune challenged animals, respectively. The present data suggest that the combination of two environmental risk factors, which have each been implicated in the etiology of major neuropsychiatric disease, induces significant but restricted neuropathological effects on hippocampal GABAergic cell populations known to be affected in brain disorders with neurodevelopmental components.
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Giovanoli
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: Liz
authors.initials: L
authors.lastname: Weber
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland. Electronic address: urmeyer@ethz.ch.
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D012741:Sexual Maturation / Q000276:immunology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D011070:Poly I-C
keywords: Animal model; Autism; Cytokines; GABA; Infection; Inflammation; Schizophrenia; Stress