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

doi:10.1038/s41398-019-0427-4

Title: Three-dimensional alteration of neurites in schizophrenia

Journal Article · Tue Feb 12 00:00:00 EST 2019 · Translational Psychiatry

DOI:https://doi.org/10.1038/s41398-019-0427-4· OSTI ID:1526003

^[1];

^[1]; Takeuchi, Akihisa ^[2];

^[2]; Terada, Yasuko ^[2]; Suzuki, Yoshio ^[3];

^[4];

^[4]; Takekoshi, Susumu ^[5]; Inomoto, Chie ^[5]; Nakamura, Naoya ^[5]; Kushima, Itaru ^[6]; Iritani, Shuji ^[6];

^[6]; Ide, Soichiro ^[7]; Ikeda, Kazutaka ^[7]; Oshima, Kenichi ^[7]; Itokawa, Masanari ^[7]; Arai, Makoto ^[7]

Tokai Univ., Kanagawa (Japan)
Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), Hyogo (Japan)
Univ. of Tokyo, Chiba (Japan)
Argonne National Lab. (ANL), Lemont, IL (United States)
Tokai Univ. School of Medicine, Kanagawa (Japan)
Nagoya Univ., Aichi (Japan)
Tokyo Metropolitan Institute of Medical Science, Tokyo (Japan)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: Japan Society for the Promotion of Science (JSPS); USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1526003

Journal Information:: Translational Psychiatry, Vol. 9, Issue 1; ISSN 2158-3188

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 21 works

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