Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: A putative model of gene × environment interaction

Desbonnet, Lieve; O’Tuathaigh, Colm M. P.; Clarke, Gerard; O’Leary, Claire; Petit, Emilie; Clarke, Niamh; Tighe, Orna; Lai, Donna; Harvey, Richard P.; Cryan, John F.; Dinan, Timothy G.; Waddington, John L.

doi:10.1016/j.bbi.2012.02.010

Cited by 75 publications

(78 citation statements)

References 81 publications

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“…NRG1-TM heterozygous knockout mice exhibited behavioral phenotypes similar to those reported by Kato et al (19). CSD-stressed NRG1-TM heterozygous knockout mice exhibited impairment of short-term memory in the Y-maze test, whereas aggressive behaviors in the social interaction test were diminished (20) (Table 1, c). These results indicate CSD exposure in NRG1-TM heterozygous knockout mice results in synergistic and additive effects on some behavioral phenotypes in adulthood.…”

Section: Nrg1 Heterozygous Knockout × Chromic Social Defeatsupporting

confidence: 69%

“…Namely, some normal and abnormal behaviors in animals with single factor were impaired and augmented or attenuated, respectively, by multiple combinations of genetic and environmental factors. The pathobiology of schizophrenia is fraught with complexity, hence the development of valid animal models for this disorder would present several challenges (20).…”

Section: Resultsmentioning

confidence: 99%

“…Desbonnet et al (20) have examined the individual and combined effects of chronic social stress during adolescence and deletion of a schizophrenic risk gene, NRG1, on adult mouse phenotype. NRG1-TM heterozygous knockout mice were stressed by CSD during adolescence, and their behavioral phenotypes were examined in adulthood.…”

Section: Nrg1 Heterozygous Knockout × Chromic Social Defeatmentioning

confidence: 99%

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Behavioral Phenotypes in Schizophrenic Animal Models With Multiple Combinations of Genetic and Environmental Factors

2013

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Abstract. Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

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Section: Nrg1 Heterozygous Knockout × Chromic Social Defeatsupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Nrg1 Heterozygous Knockout × Chromic Social Defeatmentioning

confidence: 99%

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Behavioral Phenotypes in Schizophrenic Animal Models With Multiple Combinations of Genetic and Environmental Factors

2013

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“…Approaches to develop a more useful animal model of schizophrenia have been demonstrated by the inter actions between susceptibility genes and environmental factors after the birth (89,91,92). The combination of gene mutation and viral infection before birth, i.e., pre natal treatment with polyI:C in the inducible DISC1 knockdown mice induced more apparent phenotypes for animal models of schizophrenia, such as reduced social interaction, depressivelike behavior, and anxiety like behavior, compared with either single operation (89).…”

Section: Combination Animal Modelsmentioning

confidence: 99%

Behavioral Phenotypes for Negative Symptoms in Animal Models of Schizophrenia

Miyamoto

Nitta

2014

J Pharmacol Sci

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Abstract.A devastating psychiatric disorder, schizophrenia is characterized by three major symptoms, positive and negative symptoms and cognitive deficit. Almost all current therapeutic drugs for schizophrenia have efficacy for positive symptoms, and weak efficacy for negative and cognitive deficit. In particular, social withdrawal, diminished motivation, and anhedonia as the depressive aspects of negative symptoms are resistant to the treatment of antipsychotic drugs. Therefore, there is a need for development of new therapeutic drugs for negative symptoms of schizophrenia, and it is necessary to have comprehensive animal models to understand the neuro biological foundations of their symptoms. In this review, we represent the behavioral phenotypes in available animal models of schizophrenia for drug discovery, focusing on the depressive aspects of negative symptoms. We mention here animal models based on the pathology and epidemiology of schizophrenia, e.g., the pharmacological, neurodevelopmental, genetic, and geneenvironment combination models. The animal models of schizophrenia are developed by various approaches and are assessed, but there are few models demonstrating negative symptoms with sensitivities to available therapeutic drugs. The development of comprehensive animal model reflecting negative symptoms and of novel compounds that can remedy them provide certain insight into the neuro biological process of schizophrenia and also point the way to a new therapeutic strategy.

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“…Stress during adulthood compounds the effects of in utero MIA exposure on GABAergic gene expression, including decreased expression of GAD1, and leads to dysfunctional behavior (Deslauriers et al, 2013;Giovanoli et al, 2013). Chronic social stress interacts with NRG1 deficiency to change inflammatory cytokine and BDNF gene expression (Desbonnet et al, 2012). Early life stress (Roth et al, 2009) or chronic social defeat stress (Tsankova et al, 2006) increases persistent methylation and decreases BDNF gene expression in rodents.…”

Section: Environmental Insults Disrupt Gabaergic System Developmentmentioning

confidence: 99%

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Schmidt

Mirnics

2014

Neuropsychopharmacol

196

130

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The origins of schizophrenia have eluded clinicians and researchers since Kraepelin and Bleuler began documenting their findings. However, large clinical research efforts in recent decades have identified numerous genetic and environmental risk factors for schizophrenia. The combined data strongly support the neurodevelopmental hypothesis of schizophrenia and underscore the importance of the common converging effects of diverse insults. In this review, we discuss the evidence that genetic and environmental risk factors that predispose to schizophrenia disrupt the development and normal functioning of the GABAergic system.

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Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: A putative model of gene × environment interaction

Cited by 75 publications

References 81 publications

Behavioral Phenotypes in Schizophrenic Animal Models With Multiple Combinations of Genetic and Environmental Factors

Behavioral Phenotypes in Schizophrenic Animal Models With Multiple Combinations of Genetic and Environmental Factors

Behavioral Phenotypes for Negative Symptoms in Animal Models of Schizophrenia

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

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