Taurine protects noradrenergic locus coeruleus neurons in a mouse Parkinson's disease model by inhibiting microglial M1 polarization.

Abstract:

:Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model. Taurine (150 mg/kg) was administrated (i.p) to mice 30 min prior to paraquat (10 mg/kg) and maneb (30 mg/kg) intoxication for consecutive 6 weeks (twice per week). The results clearly demonstrated that paraquat and maneb co-exposure resulted in loss of tyrosine hydroxylase-positive neurons in the LC in mice, which was significantly ameliorated by taurine. Mechanistically, inhibition of microglia-mediated neuroinflammation contributed to taurine-afforded neuroprotection. Taurine attenuated paraquat and maneb-induced microglial activation and M1 polarization as well as release of proinflammatory cytokines in brainstem of mice. Taurine also abrogated microglial NADPH oxidase activation and oxidative damage in paraquat and maneb-treated mice. Furthermore, inhibition of nuclear factor-κB (NF-κB) but not signal transducers and activators of transcription 1/3 (STAT1/3) signaling pathway participated in taurine-inhibited microglial activation. Collectively, taurine exerted LC/NE neuroprotection against microglia-mediated neurotoxicity. The robust neuroprotective effects of taurine suggest that taurine may be a promising candidate for potential therapy for patients suffering from PD.

journal_name

Amino Acids

journal_title

Amino acids

authors

Hou L,Che Y,Sun F,Wang Q

doi

10.1007/s00726-018-2547-1

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

547-556

issue

5

eissn

0939-4451

issn

1438-2199

pii

10.1007/s00726-018-2547-1

journal_volume

50

pub_type

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