Protection of MPTP-induced neuroinflammation and neurodegeneration by rotigotine-loaded microspheres.
Life Sci
; 124: 136-43, 2015 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-25640758
ABSTRACT
AIMS:
The aim of the study is to evaluate the neuroprotective effects of continuous dopaminergic stimulation (CDS) by rotigotine-loaded microspheres (RoMS) in a mouse model of MPTP-induced Parkinson's disease (PD) and to elucidate the potential mechanism underlying these effects. MAINMETHODS:
Male C57BL/6 mice were treated either intramuscularly once with RoMS or twice daily for two weeks with rotigotine, and from the 9th day, MPTP (30 mg/kg, i.p.) was injected for the last 5 days. Following treatment, Parkinsonism scores were calculated and oxidative stress-related indicators in the striatum were performed. Neuroinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected in the striatum. Expression of apoptosis-related proteins B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) was measured in the striatum by Western blot. Nigral tyrosine hydroxylase (TH)-positive neurons and microglial cell markers, i.e., ionized calcium binding adaptor molecule-1 (Iba-1) and neuronal synaptosomes, were quantified to assess the neuroprotective efficacy of RoMS. KEYFINDINGS:
The administration of rotigotine significantly improved the Parkinsonism score, protected dopaminergic neurons with antioxidants, reduced microglial cell activation and the release of neuroinflammatory cytokines, and balanced the expression of Bcl-2 and Bax in MPTP-treated mice. Interestingly, the neuroprotective properties of rotigotine were remarkably amplified by CDS treatment with RoMS.SIGNIFICANCE:
These results suggest that CDS therapy can play a neuroprotective role in an MPTP mouse model. Neuroprotective disease-modifying therapy may have the potential benefits of early treatment by normalizing compensatory mechanisms and may also help to delay dyskinesia in the later stages of PD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
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Tiofenos
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Fármacos Neuroprotetores
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Agonistas de Dopamina
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Transtornos Parkinsonianos
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Intoxicação por MPTP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2015
Tipo de documento:
Article