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Loss of Nicastrin f...
Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior
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Dries, Daniel R. (author)
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Zhu, Yi (author)
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Brooks, Mieu M. (author)
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Forero, Diego A. (author)
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Adachi, Megumi (author)
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Cenik, Basar (author)
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West, James M. (author)
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Han, Yu-Hong (author)
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Yu, Cong (author)
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Arbella, Jennifer (author)
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- Nordin, Annelie (author)
- Umeå universitet,Psykiatri
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- Adolfsson, Rolf (author)
- Umeå universitet,Psykiatri
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Del-Favero, Jurgen (author)
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Lu, Q. Richard (author)
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Callaerts, Patrick (author)
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Birnbaum, Shari G. (author)
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Yu, Gang (author)
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(creator_code:org_t)
- 2016
- 2016
- English.
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:22, s. 11647-11656
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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 gamma-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 gamma-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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dries, Daniel R.
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Zhu, Yi
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Brooks, Mieu M.
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Forero, Diego A.
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Adachi, Megumi
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Cenik, Basar
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show more...
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West, James M.
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Han, Yu-Hong
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Yu, Cong
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Arbella, Jennife ...
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Nordin, Annelie
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Adolfsson, Rolf
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Del-Favero, Jurg ...
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Lu, Q. Richard
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Callaerts, Patri ...
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Birnbaum, Shari ...
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Yu, Gang
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
- Articles in the publication
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Journal of Biolo ...
- By the university
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Umeå University