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Three-dimensional alteration of neurites in schizophrenia

Psychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Struc...

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Autores principales: Mizutani, Ryuta, Saiga, Rino, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Ide, Soichiro, Ikeda, Kazutaka, Oshima, Kenichi, Itokawa, Masanari, Arai, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372695/
https://www.ncbi.nlm.nih.gov/pubmed/30755587
http://dx.doi.org/10.1038/s41398-019-0427-4
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author Mizutani, Ryuta
Saiga, Rino
Takeuchi, Akihisa
Uesugi, Kentaro
Terada, Yasuko
Suzuki, Yoshio
De Andrade, Vincent
De Carlo, Francesco
Takekoshi, Susumu
Inomoto, Chie
Nakamura, Naoya
Kushima, Itaru
Iritani, Shuji
Ozaki, Norio
Ide, Soichiro
Ikeda, Kazutaka
Oshima, Kenichi
Itokawa, Masanari
Arai, Makoto
author_facet Mizutani, Ryuta
Saiga, Rino
Takeuchi, Akihisa
Uesugi, Kentaro
Terada, Yasuko
Suzuki, Yoshio
De Andrade, Vincent
De Carlo, Francesco
Takekoshi, Susumu
Inomoto, Chie
Nakamura, Naoya
Kushima, Itaru
Iritani, Shuji
Ozaki, Norio
Ide, Soichiro
Ikeda, Kazutaka
Oshima, Kenichi
Itokawa, Masanari
Arai, Makoto
author_sort Mizutani, Ryuta
collection PubMed
description Psychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Structures of cerebral tissues of the anterior cingulate cortex were visualized with synchrotron radiation nanotomography. Tissue constituents visualized in the three-dimensional images were traced to build Cartesian coordinate models of tissue constituents, such as neurons and blood vessels. The obtained Cartesian coordinates were used for calculating curvature and torsion of neurites in order to analyze their geometry. Results of the geometric analyses indicated that the curvature of neurites is significantly different between schizophrenia and control cases. The mean curvature of distal neurites of the schizophrenia cases was ~1.5 times higher than that of the controls. The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene, suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. It has been shown that the anterior cingulate cortex analyzed in this study has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia.
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spelling pubmed-63726952019-02-15 Three-dimensional alteration of neurites in schizophrenia Mizutani, Ryuta Saiga, Rino Takeuchi, Akihisa Uesugi, Kentaro Terada, Yasuko Suzuki, Yoshio De Andrade, Vincent De Carlo, Francesco Takekoshi, Susumu Inomoto, Chie Nakamura, Naoya Kushima, Itaru Iritani, Shuji Ozaki, Norio Ide, Soichiro Ikeda, Kazutaka Oshima, Kenichi Itokawa, Masanari Arai, Makoto Transl Psychiatry Article Psychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Structures of cerebral tissues of the anterior cingulate cortex were visualized with synchrotron radiation nanotomography. Tissue constituents visualized in the three-dimensional images were traced to build Cartesian coordinate models of tissue constituents, such as neurons and blood vessels. The obtained Cartesian coordinates were used for calculating curvature and torsion of neurites in order to analyze their geometry. Results of the geometric analyses indicated that the curvature of neurites is significantly different between schizophrenia and control cases. The mean curvature of distal neurites of the schizophrenia cases was ~1.5 times higher than that of the controls. The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene, suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. It has been shown that the anterior cingulate cortex analyzed in this study has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia. Nature Publishing Group UK 2019-02-12 /pmc/articles/PMC6372695/ /pubmed/30755587 http://dx.doi.org/10.1038/s41398-019-0427-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mizutani, Ryuta
Saiga, Rino
Takeuchi, Akihisa
Uesugi, Kentaro
Terada, Yasuko
Suzuki, Yoshio
De Andrade, Vincent
De Carlo, Francesco
Takekoshi, Susumu
Inomoto, Chie
Nakamura, Naoya
Kushima, Itaru
Iritani, Shuji
Ozaki, Norio
Ide, Soichiro
Ikeda, Kazutaka
Oshima, Kenichi
Itokawa, Masanari
Arai, Makoto
Three-dimensional alteration of neurites in schizophrenia
title Three-dimensional alteration of neurites in schizophrenia
title_full Three-dimensional alteration of neurites in schizophrenia
title_fullStr Three-dimensional alteration of neurites in schizophrenia
title_full_unstemmed Three-dimensional alteration of neurites in schizophrenia
title_short Three-dimensional alteration of neurites in schizophrenia
title_sort three-dimensional alteration of neurites in schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372695/
https://www.ncbi.nlm.nih.gov/pubmed/30755587
http://dx.doi.org/10.1038/s41398-019-0427-4
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