| Outline of Annual Research Achievements |
First, we mapped neural circuit dysplasia by next-generation diffusion MRI analysis including diffusion tensor and three-dimensional construction of confocal images of transparent brain. By combining the innovative brain clearing technology and cutting-edge MRI technology proposed in recent years, this research has not only elucidated the function of sulfatase in axon guidance, but also a new neuropsychiatric disorder with minute structural abnormalities. Contributes to the search for surrogate markers.
In a recently published manuscript we analyzed commissural fibers in the brains of Sulf1/2 DKO mice using radiological and histological methods. Using fiber tractography analysis, we found abnormalities in the commissural fiber system of the CC and DHC and confirmed these histological abnormalities by FluoroMyelin staining and anterograde tracing of the DHC fibers. Our MR analysis revealed a significantly fewer number of streamlines in both the CC and DHC. Analysis by confocal microscopy confirmed that the CC size was reduced in Sulf1/2 DKO mice. Furthermore, histological analyses revealed that the area of DHC remained unchanged while some fibers of the DHC appeared to cross the midline at more rostral levels. These results indicate that Sulf1/2 play an important role in the normal development of commissural fibers.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We published the following article.
Tsuji, Y., Kerever, A., Furukawa, T., Kamagata, K., Saito, Y., Aoki, S., Hata, J., Okano, H., Kobayashi, K., Okada, T., Miya, K., Keino-Masu, K., Masu, M., & Arikawa-Hirasawa, E. (2022) Diffusion magnetic resonance tractography-based evaluation of commissural fiber abnormalities in a heparan sulfate endosulfatase-deficient mouse brain. Magn. Reson. Imaging, 88, 123-131.
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| Strategy for Future Research Activity |
We plan to further investigate non commissural fibers in the Sulf1 / 2 DKO. In addition, we plan to investigate commissural and non commissural fibers in the single KO animals (Sulf1 KO and Sulf2 KO) to examine the individual roles of Sulf1 and Sulf2. Previous studies did not detect significant axonal abnormalities in Sulf1 KO and Sulf2 KO mice. However, the accuracy of the analysis found by diffusion MRI analysis in connection with confocal microscopy makes it possible to determine small axonal events that may have been previously overlooked due to poor detection sensitivity.
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| Causes of Carryover |
Due to Covid 19, research activities were restricted, some reagents could not be delivered, and some experiments were carried over to the following year. In addition, attending international meetings was not possible.
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