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Animal Models

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Animal Model: Prenatal Immune Challenge: PolyI:C (Delivery Timing Varies)
Preparation Type: Developmental Preparations
DA-related behavior: No change in total distance traveled in open field but reduced center exploration; increased response to amphetamine and MK-801 (emerges after puberty; not rescued by cross-fostering)
Gating: Disrupted PPI (post-puberty; deficits not rescued by cross-fostering)
Cognitive behavior: Reduced escape latency in Morris water maze; impairment in novel object recognition memory; deficits in latent inhibition (post-puberty; deficits not rescued by cross-fostering); electrophysiology: reduced theta oscillation generated in the CA1 area of the hippocampus
Social behavior: Reduced social interaction
Molecular/morphological signature: Increased DA turnover and reduced binding to D2 receptors in striatum; reduced reelin- and parvalbumin- expressing neurons in PFC; reduced DA levels and D1 receptors in PFC; increased TH expression in striatum; reduced density of cerebellar Purkinje cells; delayed myelination of hippocampus; reduced parvalbumin-expressing neurons in the hippocampus; enlargement of lateral ventricles; impaired synaptic development of upper-layer neurons
Response to APD: Disrupted PPI was improved by clozapine and chlorpromazine; deficits in latent inhibition and novel object recognition memory were improved by clozapine but not haloperidol; deficits in Morris water maze were improve by clozapine
Citations: Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH. Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun . 2009 Jan ; 23(1):116-23. Abstract

Meyer U, Knuesel I, Nyffeler M, Feldon J. Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis. Psychopharmacology (Berl). 2010;208(4):531-43. Abstract

Meyer U, Schwendener S, Feldon J, Yee BK. Prenatal and postnatal maternal contributions in the infection model of schizophrenia. Exp Brain Res . 2006 Aug 1 ; 173(2):243-57. Abstract

Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J. Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology . 2008 Jan ; 33(2):441-56. Abstract

Ozawa K, Hashimoto K, Kishimoto T, Shimizu E, Ishikura H, Iyo M. Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia. Biol Psychiatry . 2006 Mar 15 ; 59(6):546-54. Abstract

Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci . 2007 Oct 3 ; 27(40):10695-702. Abstract

Makinodan M, Tatsumi K, Manabe T, Yamauchi T, Makinodan E, Matsuyoshi H, Shimoda S, Noriyama Y, Kishimoto T, Wanaka A. Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring. J Neurosci Res . 2008 Aug 1 ; 86(10):2190-200. Abstract

Li Q, Cheung C, Wei R, Hui ES, Feldon J, Meyer U, Chung S, Chua SE, Sham PC, Wu EX, McAlonan GM. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model. PLoS One. 2009;4(7):e6354. Abstract

Bitanihirwe BK, Peleg-Raibstein D, Mouttet F, Feldon J, Meyer U. Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia. Neuropsychopharmacology. 2010;35(12):2462-78. Abstract

Ducharme G, Lowe GC, Goutagny R, Williams S. Early alterations in hippocampal circuitry and theta rhythm generation in a mouse model of prenatal infection: implications for schizophrenia. PLoS One. 2012;7(1):e29754. Abstract

Soumiya H, Fukumitsu H, Furukawa S. Prenatal immune challenge compromises development of upper-layer but not deeper-layer neurons of the mouse cerebral cortex. J Neurosci Res. 2011;89(9):1342-50. Abstract

November 28, 2015
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