Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson's Animal Model.
Mol Imaging Biol
; 22(4): 1031-1042, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32086763
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Receptor de Fator Estimulador de Colônias de Macrófagos
/
Microglia
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Fármacos Neuroprotetores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Imaging Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Coréia do Sul