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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 4/2020

01-08-2020 | Positron Emission Tomography | Research Article

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

Authors: 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

Published in: Molecular Imaging and Biology | Issue 4/2020

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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.
Appendix
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Metadata
Title
Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson’s Animal Model
Authors
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
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 4/2020
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-020-01485-w

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