Amiloride is neuroprotective in an MPTP model of Parkinson's disease

被引：105

作者：

Arias, Robert L. ^{[1
]}

Sung, Mei-Li A. ^{[1
]}

Vasylyev, Dmytro ^{[1
]}

Zhang, Mei-Yi ^{[1
]}

Albinson, Kristin ^{[1
]}

Kubek, Katie ^{[1
]}

Kagan, Natasha ^{[1
]}

Beyer, Chad ^{[1
]}

Lin, Qian ^{[1
]}

Dwyer, Jason M. ^{[1
]}

Zaleska, Margaret M. ^{[1
]}

Bowlby, Mark R. ^{[1
]}

Dunlop, John ^{[1
]}

Monaghan, Michael ^{[1
]}

机构：

[1] Wyeth Discovery Neurosci, Princeton, NJ USA

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 31卷 / 03期

关键词：

MPTP; amiloride; psalmotoxin; substantia nigra; Parkinson's disease; dopamine transporter; tyrosine hydroxylase; ASIC;

D O I：

10.1016/j.nbd.2008.05.008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The diuretic amiloride has recently proven neuroprotective in models of cerebral ischemia, a property attributable to the drug's inhibition of central acid-sensing ion channels (ASICs). Given that Parkinson's disease (PD), like ischemia, is associated with cerebral lactic acidosis, we tested amiloride in the MPTP-treated mouse, a model of PD also manifesting lactic acidosis. Amiloride was found to protect substantia nigra (SNc) neurons from MPTP-induced degeneration, as determined by attenuated reductions in striatal tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunohistochemistry, as well as smaller declines in striatal DAT radioligand binding and dopamine levels. More significantly, amiloride also preserved dopaminergic cell bodies in the SNc. Administration of psalmotoxin venom (PcTX), an ASIC1a blocker, resulted in a much more modest effect, attenuating only the deficits in striatal DAT binding and dopamine. These findings represent the first experimental evidence of a potential role for ASICs in the pathogenesis of Parkinson's disease. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：334 / 341

页数：8

共 59 条

[1] Parkinsonism genes: culprits and clues [J].