Title

Neuroprotective And Anti-Inflammatory Properties Of A Coffee Component In The Mptp Model Of Parkinson'S Disease

Keywords

Anti-inflammatory; Antioxidant; Astrocytes; Eicosanoyl-5-hydroxytryptamide; Microglia; Neuroprotection

Abstract

Consumption of coffee is associated with reduced risk of Parkinson's disease (PD), an effect that has largely been attributed to caffeine. However, coffee contains numerous components that may also be neuroprotective. One of these compounds is eicosanoyl-5-hydroxytryptamide (EHT), which ameliorates the phenotype of α-synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation. Here, we sought to investigate if EHT has an effect in the MPTP model of PD. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. In cultured primary microglia and astrocytes, EHT had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, iNOS induction, and nitric oxide production. EHT also exhibited a robust anti-oxidant activity in vitro. Additionally, in SH-SY5Y cells, MPP+-induced demethylation of phosphoprotein phosphatase 2A (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT. These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti-inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A. Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD. © 2013 The American Society for Experimental NeuroTherapeutics, Inc.

Publication Date

1-1-2013

Publication Title

Neurotherapeutics

Volume

10

Issue

1

Number of Pages

143-153

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s13311-012-0165-2

Socpus ID

84873157042 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84873157042

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