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Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson’s Animal Model

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Abstract

Purpose

Neuroinflammation in Parkinson’s disease (PD) is known to play a pivotal role in progression to neuronal degeneration. It has been reported that colony-stimulation factor 1 receptor (CSF-1R) inhibition can effectively deplete microglia. However, its therapeutic efficacy in PD is unclear still now.

Procedures

To elucidate this issue, we examined the contribution of microglial depletion to PD by behavioral testing, positron emission tomography (PET) imaging, and immunoassays in sham, PD, and microglial depletion PD model (PLX3397 was administered to PD groups, with n = 6 in each group).

Results

The microglial depletion in PD model showed improved sensory motor function and depressive-like behavior. NeuroPET revealed that PLX3397 treatment resulted in partial recovery of striatal neuro-inflammatory functions (binding values of [18F]DPA-174 for PD, 1.47 ± 0.12, p < 0.01 vs. for PLX3397 in PD: 1.33 ± 0.26) and the dopaminergic (binding values of 18F-FP-CIT for PD, 1.32 ± 0.07 vs. for PLX3397 in PD: 1.54 ± 0.10, p < 0.01) and glutamatergic systems (binding values of [18F]FPEB for PD: 9.22 ± 0.54 vs. for PLX3397 Tx in PD: 9.83 ± 0.96, p > 0.05). Western blotting for microglia showed similar changes.

Conclusion

Microglial depletion has inflammation-related therapeutic effects, which have beneficial effects on motor and nonmotor symptoms of PD.

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Funding

This research was supported by a grant from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea (50536-2020).

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Authors and Affiliations

  1. Division of Applied RI, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, South Korea

    Se Jong Oh, Heesu Ahn, Ki-Hye Jung, Sang Jin Han, Kyung Rok Nam, Kyung Jun Kang, Ji-Ae Park, Kyo Chul Lee, Yong Jin Lee & Jae Yong Choi

  2. Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea

    Heesu Ahn

  3. Medical Device-Bio Research Institute, Korea Testing and Research Institute, Gwacheon, Gyeonggi-do, South Korea

    Ki-Hye Jung

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  1. Se Jong Oh
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Oh, S.J., Ahn, H., Jung, KH. et al. Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson’s Animal Model. Mol Imaging Biol 22, 1031–1042 (2020). https://doi.org/10.1007/s11307-020-01485-w

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