title: Prenatal immune activation in mice blocks the effects of environmental enrichment on exploratory behavior and microglia density.
abstract: Adverse environmental factors including prenatal maternal infection are capable of inducing long-lasting behavioral and neural alterations which can enhance the risk to develop schizophrenia. It is so far not clear whether supportive postnatal environments are able to modify such prenatally-induced alterations. In rodent models, environmental enrichment influences behavior and cognition, for instance by affecting endocrinologic, immunologic, and neuroplastic parameters. The current study was designed to elucidate the influence of postnatal environmental enrichment on schizophrenia-like behavioral alterations induced by prenatal polyI:C immune stimulation at gestational day 9 in mice. Adult offspring were tested for amphetamine-induced locomotion, social interaction, and problem-solving behavior as well as expression of dopamine D1 and D2 receptors and associated molecules, microglia density and adult neurogenesis. Prenatal polyI:C treatment resulted in increased dopamine sensitivity and dopamine D2 receptor expression in adult offspring which was not reversed by environmental enrichment. Prenatal immune activation prevented the effects of environmental enrichment which increased exploratory behavior and microglia density in NaCl treated mice. Problem-solving behavior as well as the number of immature neurons was affected by neither prenatal immune stimulation nor postnatal environmental enrichment. The behavioral and neural alterations that persist into adulthood could not generally be modified by environmental enrichment. This might be due to early neurodevelopmental disturbances which could not be rescued or compensated for at a later developmental stage.
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Buschert
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany.
authors.forename: Marna E
authors.initials: ME
authors.lastname: Sakalem
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany.
authors.forename: Roja
authors.initials: R
authors.lastname: Saffari
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Hohoff
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany; Department of Psychiatry, St. Rochus-Hospital, Telgte, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Germany.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Germany. Electronic address: ambree@uni-muenster.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambrée
mesh_terms: D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007369:Interferon Inducers / Q000633:toxicity; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000451:nursing* / Q000473:pathology* / Q000503:physiopathology*; D011340:Problem Solving / Q000187:drug effects; D011954:Receptors, Dopamine / Q000378:metabolism; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D007369:Interferon Inducers; D011954:Receptors, Dopamine; D000661:Amphetamine; D011070:Poly I-C; D003345:Corticosterone
keywords: Environmental enrichment; Maternal immune stimulation; Mouse model; PolyI:C; Schizophrenia