Inhibition of Rho-kinase by Fasudil protects dopamine neurons and attenuates inflammatory response in an intranasal lipopolysaccharide-mediated Parkinson's model.
Eur J Neurosci
; 43(1): 41-52, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26565388
ABSTRACT
Microglia activation and inflammatory factors in brain microenvironment are associated with degeneration of neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients and various PD models. There is increasing evidence that the Rho/ROCK (Rho kinase) signalling pathway may play a critical role in the inflammatory response, and ROCK inhibitor has been reported to have neuroprotective effects. In this study, we examined the neuroprotective potential and possible mechanism of ROCK inhibitor Fasudil in an intranasal lipopolysaccharide (LPS)-induced PD model. ROCK was activated with LPS stimulation and inhibited by Fasudil treatment in this PD model. Behavioural tests demonstrated a clear improvement in motor performance after Fasudil treatment. Furthermore, Fasudil resulted in a significant attenuation of dopamine cell loss, α-synuclein accumulation and inflammatory response with the reversion of inflammatory M1 to anti-inflammatory M2 microglia, decreased NF-кB activation, and IL-12 and TNF-α generation in the SN and olfactory bulb in this model. This study establishes a role for Fasudil in protecting against LPS-mediated dopamine degeneration and provides a therapeutic strategy for the treatment of PD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Neuroprotetores
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina
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Transtornos Parkinsonianos
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Encefalite
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Quinases Associadas a rho
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Neurônios Dopaminérgicos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article