ArticleThe Journal of biological chemistry2016
Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Dysregulation of myelination-related genes in schizophrenia.Journal of neurochemistry · 2024Review
- Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.Molecular psychiatry · 2024Article
- Influenza A virus infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse.Journal of neuroinflammation · 2023Article
- In Vivo Clonal Analysis Reveals Development Heterogeneity of Oligodendrocyte Precursor Cells Derived from Distinct Germinal Zones.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Maternal high-fat diet modifies myelin organization, microglial interactions, and results in social memory and sensorimotor gating deficits in adolescent mouse offspring.Brain, behavior, & immunity - health · 2021Article
- Pen-2 Negatively Regulates the Differentiation of Oligodendrocyte Precursor Cells into Astrocytes in the Central Nervous System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Oligodendrocyte lineage cells and depression.Molecular psychiatry · 2021Review
- Early-life stress impairs postnatal oligodendrogenesis and adult emotional behaviour through activity-dependent mechanisms.Molecular psychiatry · 2020Article
- Bad wrap: Myelin and myelin plasticity in health and disease.Developmental neurobiology · 2018Review
- Olig2 Silence Ameliorates Cuprizone-Induced Schizophrenia-Like Symptoms in Mice.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- The neurobiology of transition to psychosis: clearing the cache.Journal of psychiatry & neuroscience : JPN · 2017Article
- Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin.PloS one · 2017Article
- Heterogeneity in oligodendroglia: Is it relevant to mouse models and human disease?Journal of neuroscience research · 2016Review
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of γ-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate γ-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia.
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Registered trials
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