Systemic administration of neuregulin-1β1 protects dopaminergic neurons in a mouse model of Parkinson's disease

被引：65

作者：

Carlsson, Thomas ^{[1
]}

Schindler, Friederike R. ^{[1
]}

Hoellerhage, Matthias ^{[1
]}

Depboylu, Candan ^{[1
]}

Arias-Carrion, Oscar ^{[1
]}

Schnurrbusch, Stefan ^{[1
]}

Roesler, Thomas W. ^{[1
]}

Wozny, Wojciech ^{[2
]}

Schwall, Gerhard P. ^{[2
]}

Groebe, Karlfried ^{[2
]}

Oertel, Wolfgang H. ^{[1
]}

Brundin, Patrik ^{[3
]}

Schrattenholz, Andre ^{[2
]}

Hoeglinger, Guenter U. ^{[1
]}

机构：

[1] Univ Marburg, Dept Neurol, D-35039 Marburg, Germany

[2] ProteoSys AG, Mainz, Germany

[3] Lund Univ, Wallenberg Neurosci Ctr, Dept Expt Med Sci, Neuronal Survival Unit, Lund, Sweden

来源：

JOURNAL OF NEUROCHEMISTRY | 2011年 / 117卷 / 06期

关键词：

dopamine; ErbB4; receptor; neuregulin; neuroprotection; Parkinson's disease; NEUROTROPHIC FACTOR; RECEPTOR; EXPRESSION; ERBB4; PATHWAYS; INFUSION; 6-OHDA; BRAIN; GDNF; MPTP;

D O I：

10.1111/j.1471-4159.2011.07284.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

P>Neuregulin-1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood-brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson's disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1 beta(1) (Nrg1 beta(1)-ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1 beta(1)-ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1 beta(1)-ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1 beta(1)-ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson's disease patients.

引用

页码：1066 / 1074

页数：9

共 36 条

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