Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson’s Animal Model
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 stil...
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Published in | Molecular imaging and biology Vol. 22; no. 4; pp. 1031 - 1042 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.08.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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 [
18
F]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
18
F-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 [
18
F]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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1536-1632 1860-2002 |
DOI: | 10.1007/s11307-020-01485-w |