Rewiring the brain: remote-controlled axon guidance by magnetic nanoparticles to improve Parkinson's therapies
| Project/Area Number |
22K06430
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
土井 大輔 京都大学, iPS細胞研究所, 特定拠点講師 (10587851)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Parkinson's Disease / Magnetic Nanoparticle / Cell Replacment / Stem Cells / Dopaminergic Neurons / Dopaminergic neurons / Stem cells (iPSCs) / Magnetic nanoparticles / Halbach magnet / Axon guidance / CNS regeneration / Parkinson's disease / Nanotechnology / Cell Replacement Therapy / Magnetic Nanoparticles / Pluripotent Stem Cells / Neuronal Regeneration |
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| Outline of Research at the Start |
To rewire the brain, we aim for the remote-controlled guidance of neurite growth by magnetic nanoparticles (MNPs). When an external magnetic field is applied, these MNPs generate forces at the cell membrane which promote neurite growth and increase neurite extension in the direction of the magnetic field.
The aim is to adept this system for single induced dopaminergic neurons and neurospheres. We will use the obtained knowledge and transplant the MNP-loaded neurospheres in Parkinson’s disease model rats to rewire the disconnected brain regions.
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| Outline of Annual Research Achievements |
In the FY2023, large efforts were made towards the magnetic manipulation of nanoparticle-loaded dopaminergic neurospheres. In close collaboration with the Raffa Lab (Pisa, Italy) we were able to show the asymmetric neurite growth in direction of the magnetic field.
As the transition to animal models requires further optimization, we performed the magnetic manipulation in ex vivo cultures. These cultures are 350 um thick sections of the mouse brain. Nanoparticle=loaded spheres were grafted into these ex vivo cultures. We were able to see neurite growth in the direction of the magnetic field.
In summary, in the FY2023, we were able to translate our approach to the neurosphere model and were able to show that the stretch growth is still presence in an organotypic environment.
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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
As mentioned above, we were able to tackle the two major points proposed for FY2023. On the one hand, the magnetic manipulation of neurospheres was done. On the other hand, the first step towards the application of our approach in vivo was tested. Now, the actual application in vivo can be tested.
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| Strategy for Future Research Activity |
The first step is generating more data with our neurosphere and ex vivo ex vivo model. After optimizing the parameters, we can translate the approach to the animal model. Here, the biggest task is to finalize designing an appropriate magnetic applicator.
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Report
(2 results)
Research Products
(10 results)
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[Presentation] Spatiotemporal control of RAS pathway activation by biofunctionalized nanoparticles for guided neurite growth, maturation, and regeneration2022
Author(s)
Fabian Raudzus (presenter), Hendrik Schoeneborn, Sebastian Neumann, Hiromasa Adachi, Emilie Secret, Oliver Brylski, Christine Menager, Jean-Michel Siaugue, Rolf Heumann, Jun Takahashi
Organizer
Horizons in Neuroscience: Organoids, Optogenetics and Remote Control - German Society for Biochemistry and Molecular Biology (GBM e.V.)
Related Report
Int'l Joint Research / Invited
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