Disc1

Narayan, Soumya; Nakajima, Kazunori; Sawa, Akira

doi:10.1177/1073858412470168

Cited by 35 publications

(20 citation statements)

References 153 publications

(205 reference statements)

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“…Additionally, Disc1 -LI mice show aberrant trafficking of amyloid precursor protein (APP) in cortical neurons, which leads to aberrant C-terminal processing of APP and A-beta peptide generation (Shahani et al, 2015). These findings are in good agreement with the role of Disc1 in neuronal development and function revealed by previous cell biological studies (Brandon and Sawa, 2011; Narayan et al, 2013). …”

Section: Haploinsufficiency Modelssupporting

confidence: 93%

Utility and validity of DISC1 mouse models in biological psychiatry

et al. 2016

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We have seen an era of explosive progress in translating neurobiology into etiological understanding of mental disorders for the past 10–15 years. The discovery of Disrupted-in-schizophrenia 1 (DISC1) gene was one of major driving forces that have contributed to the progress. The finding that DISC1 plays crucial roles in neurodevelopment and synapse regulation clearly underscored the utility and validity of DISC1-related biology in advancing our understanding of pathophysiological processes underlying psychiatric conditions. Despite recent genetic studies that failed to identify DISC1 as a risk gene for sporadic cases of schizophrenia, DISC1 mutant mice, coupled with various environmental stressors, have proven successful in satisfying face validity as models of a wide range of human psychiatric conditions. Investigating mental disorders using these models is expected to further contribute to the circuit-level understanding of the pathological mechanisms, as well as to the development of novel therapeutic strategies in the future.

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Section: Haploinsufficiency Modelssupporting

confidence: 93%

Utility and validity of DISC1 mouse models in biological psychiatry

et al. 2016

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“…Robo1 interacts with Slit1 to regulate the dendritic branching of cortical neurons [47]. Disc1 proteins play an important role in various stages of neural development [1,48]. Altered dendritic architecture has been observed in the mPFC and DG neurons of Disc1 knockout mice [37,49].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Infection Affects the Neuronal Architecture and Cognitive Function in Adult Mice

Li¹,

Chang²,

Lee

et al. 2014

Dev Neurosci

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Environmental factors such as prenatal infection are involved in the pathogenic processes of neurodevelopmental psychiatric disorders. In the present study, we administered a viral mimic, polyriboinosinic-polyribocytidylic acid (poly I:C, 20 mg/kg, i.p.), to pregnant B6 mice at gestational day 9.5. Neonates born to these poly I:C-treated dams showed an increase of microglia in the hippocampus, indicating an activation of the immune system in the brains. Moreover, a significant increase in the number of dopamine-producing neurons in the ventral tegmental area was observed in adult male poly I:C offspring compared with age-matched saline offspring. Poly I:C offspring also exhibited hypolocomotor activity in a novel open-field arena but did not display signs of anxiety or depression in the elevated plus maze or the forced swim test, respectively. However, the short-term memory of the poly I:C offspring was impaired in a novel object recognition task. Therefore, the dendritic architecture of granule cells in the dentate gyrus (DG) and pyramidal neurons in the medial prefrontal cortex (mPFC) were examined. The dendritic complexity was reduced in the DG granule cells of the poly I:C offspring and exhibited shorter dendritic length compared with the saline offspring. The density of dendritic spines in the DG granule cells was also decreased in the poly I:C offspring. Furthermore, the dendritic complexity and spine density were reduced in layer II/III mPFC pyramidal neurons of the poly I:C offspring. Together, these data demonstrate impaired short-term memory and altered dendritic architecture in adult poly I:C offspring, which validates the prenatal infection paradigm as a model for neurodevelopmental psychiatric disorders.

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“…DISC1 plays a major role in early brain development by regulating a number of essential neurodevelopmental events including cell proliferation, neurite outgrowth, synapse formation and neuronal migration 194,195 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%