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Title: Three-dimensional alteration of neurites in schizophrenia

Abstract

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 similar to 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 studymore » has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia.« less

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2]; ORCiD logo [2];  [2];  [3]; ORCiD logo [4]; ORCiD logo [4];  [5];  [5];  [5];  [6];  [6]; ORCiD logo [6];  [7];  [7];  [7];  [7];  [7]
  1. Tokai Univ., Kanagawa (Japan)
  2. Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), Hyogo (Japan)
  3. Univ. of Tokyo, Chiba (Japan)
  4. Argonne National Lab. (ANL), Lemont, IL (United States)
  5. Tokai Univ. School of Medicine, Kanagawa (Japan)
  6. Nagoya Univ., Aichi (Japan)
  7. Tokyo Metropolitan Institute of Medical Science, Tokyo (Japan)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
Japan Society for the Promotion of Science (JSPS); USDOE
OSTI Identifier:
1526003
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Translational Psychiatry
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2158-3188
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

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, and Arai, Makoto. Three-dimensional alteration of neurites in schizophrenia. United States: N. p., 2019. Web. doi:10.1038/s41398-019-0427-4.
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. United States. doi:10.1038/s41398-019-0427-4.
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, and Arai, Makoto. Tue . "Three-dimensional alteration of neurites in schizophrenia". United States. doi:10.1038/s41398-019-0427-4. https://www.osti.gov/servlets/purl/1526003.
@article{osti_1526003,
title = {Three-dimensional alteration of neurites in schizophrenia},
author = {Mizutani, Ryuta and Saiga, Rino and Takeuchi, Akihisa and Uesugi, Kentaro and Terada, Yasuko and Suzuki, Yoshio and De Andrade, Vincent and De Carlo, Francesco and Takekoshi, Susumu and Inomoto, Chie and Nakamura, Naoya and Kushima, Itaru and Iritani, Shuji and Ozaki, Norio and Ide, Soichiro and Ikeda, Kazutaka and Oshima, Kenichi and Itokawa, Masanari and Arai, Makoto},
abstractNote = {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 similar to 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.},
doi = {10.1038/s41398-019-0427-4},
journal = {Translational Psychiatry},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {2}
}

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Figures / Tables:

Figure 1 Figure 1: Three-dimensional visualization of cerebral cortex neurons and their models represented with Cartesian coordinates. The pial surface is toward the top. The three-dimensional image was rendered with VGStudio (Volume Graphics, Germany). The models were drawn using MCTrace60. Structural constituents of the model are color-coded. Nodes composing each constituent aremore » indicated with circles. Dots indicate soma nodes. a Rendering of dataset N2C of the control N2 tissue. Voxel values of 500–1600 were rendered with the scatter HQ algorithm. Scale bar: 20 μm. b Initial model. Structures of somata and thick neurites were built manually in order to mask them in the subsequent automatic model generation. c Automatically generated model of the tissue structure. Neurites were searched by calculating the gradient vector flow61 throughout the image. The neurites found in the search were then traced using a three-dimensional Sobel filter62. d The computer-generated model was manually examined and edited according to the method used in protein crystallography. The obtained working model was refined with conjugate gradient minimization. The geometric parameters were calculated from the three-dimensional Cartesian coordinates of the refined model. e Stereo drawing of a spiny dendrite indicated with the arrow head in d. The structure is superposed on a three-dimensional map of the observed image. The map drawn in gray is contoured at 2.5 times the standard deviation (2.5 σ) of the image intensity with a grid size of 96.6 nm« less

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