Global ETD Search

1	Animal Models of Prophylaxis and Prevention of Schizophrenia: Prenatal Seasonal Influenza Vaccine and Postnatal Valproate Doucet, Jean-Sebastien 21 November 2012 (has links) Schizophrenia is a mental illness with early adult onset. Prophylactic treatments would be clinically important and therefore we investigated the effect of two interventions: influenza vaccination of pregnant mothers and valproate treatment during late adolescence. Maternal immune response during pregnancy is thought to adversely affect brain development. We sought to assess whether immune activation by influenza vaccine could itself cause behavioural abnormalities in a mouse model. Our data suggest that further work is needed to make firm conclusions about the behavioural effects of the influenza vaccine. The second part of this thesis describes an analysis of valproate treatment on cortical neuron morphology in Disc1 L100P mice, a model for schizophrenia. Valproate was previously shown to prevent the onset of abnormal behaviours in Disc1 L100P mice. Contrary to expectations, valproate decreased apical spine density and the number of dendritic processes rather than reversing the dendritic deficits seen in Disc1 L100P mice. Valproate Disc1 MIA influenza Disc1 L100P Valproic Acid VPA Schizophrenia maternal immune activation neurodevelopment prenatal mouse pregnancy vaccine behaviour IL-6 postnatal pyramidal neuron cortex morphology 0419 0317
2	Animal Models of Prophylaxis and Prevention of Schizophrenia: Prenatal Seasonal Influenza Vaccine and Postnatal Valproate Doucet, Jean-Sebastien 21 November 2012 (has links) Schizophrenia is a mental illness with early adult onset. Prophylactic treatments would be clinically important and therefore we investigated the effect of two interventions: influenza vaccination of pregnant mothers and valproate treatment during late adolescence. Maternal immune response during pregnancy is thought to adversely affect brain development. We sought to assess whether immune activation by influenza vaccine could itself cause behavioural abnormalities in a mouse model. Our data suggest that further work is needed to make firm conclusions about the behavioural effects of the influenza vaccine. The second part of this thesis describes an analysis of valproate treatment on cortical neuron morphology in Disc1 L100P mice, a model for schizophrenia. Valproate was previously shown to prevent the onset of abnormal behaviours in Disc1 L100P mice. Contrary to expectations, valproate decreased apical spine density and the number of dendritic processes rather than reversing the dendritic deficits seen in Disc1 L100P mice. Valproate Disc1 MIA influenza Disc1 L100P Valproic Acid VPA Schizophrenia maternal immune activation neurodevelopment prenatal mouse pregnancy vaccine behaviour IL-6 postnatal pyramidal neuron cortex morphology 0419 0317
3	Disc1 Mutant Mice Subjected to Chronic Social Defeat Stress as a Model of Gene-Environment Interaction in Schizophrenia and Depression Haque, F. Nipa 25 January 2010 (has links) Human genetic data suggests DISC1 (Disrupted-in-schizophrenia 1) is a susceptibility gene for schizophrenia and depression. Disc1 Q31L-/- mutants show depression-like behaviour and Disc1 L100P-/- mutants schizophrenia-like behaviour. Heterozygous mutants show an intermediate phenotype. In a gene-environment interaction study, we exposed heterozygotes to chronic social defeat (CSD) stress and phenotyped behaviour. Disc1, Bdnf(III) and Pde4b mRNA levels were also measured. Moreover, as epigenetic mechanisms may mediate some effects of CSD, we also exposed wildtype mice to CSD concurrently with the histone deacetylase inhibitor valproate. We found that CSD increased anxiety in L100P-/+ mutants, and that levels of Disc1, Bdnf(III) and Pde4b mRNA were higher in this mutant. Valproate treatment did not correct CSD-induced behavioural changes. In conclusion, we have demonstrated an interaction between a strong susceptibility gene for psychiatric disease and an environmental manipulation similar to stressors known to affect mental illness. gene-environment interaction social defeat Disc1 mutant mice schizophrenia depression animal model disrupted-in-schizophrenia 1 (Disc1) brain-derived neurotrophic factor (Bdnf) phosphodiesterase 4b (Pde4b) valproate histone deacetylase (HDAC) epigenetics Q31L L100P 0317 0384 0347
4	Disc1 Mutant Mice Subjected to Chronic Social Defeat Stress as a Model of Gene-Environment Interaction in Schizophrenia and Depression Haque, F. Nipa 25 January 2010 (has links) Human genetic data suggests DISC1 (Disrupted-in-schizophrenia 1) is a susceptibility gene for schizophrenia and depression. Disc1 Q31L-/- mutants show depression-like behaviour and Disc1 L100P-/- mutants schizophrenia-like behaviour. Heterozygous mutants show an intermediate phenotype. In a gene-environment interaction study, we exposed heterozygotes to chronic social defeat (CSD) stress and phenotyped behaviour. Disc1, Bdnf(III) and Pde4b mRNA levels were also measured. Moreover, as epigenetic mechanisms may mediate some effects of CSD, we also exposed wildtype mice to CSD concurrently with the histone deacetylase inhibitor valproate. We found that CSD increased anxiety in L100P-/+ mutants, and that levels of Disc1, Bdnf(III) and Pde4b mRNA were higher in this mutant. Valproate treatment did not correct CSD-induced behavioural changes. In conclusion, we have demonstrated an interaction between a strong susceptibility gene for psychiatric disease and an environmental manipulation similar to stressors known to affect mental illness. gene-environment interaction social defeat Disc1 mutant mice schizophrenia depression animal model disrupted-in-schizophrenia 1 (Disc1) brain-derived neurotrophic factor (Bdnf) phosphodiesterase 4b (Pde4b) valproate histone deacetylase (HDAC) epigenetics Q31L L100P 0317 0384 0347

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