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Systemic administration of Neuregulin-1ß(1) protects dopaminergic neurons in a mouse model of Parkinson's disease.

Carlsson, Thomas; Schindler, Friederike R; Höllerhage, Matthias; Depboylu, Candan; Arias-Carrión, Oscar; Schnurrbusch, Stefan; Rösler, Thomas W; Wozny, Wojciech; Schwall, Gerhard P and Groebe, Karlfried, et al. (2011) In Journal of Neurochemistry 117(6). p.1066-1074
Abstract
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 Nrg1ß(1) (Nrg1ß(1) -ECD) increased dopamine levels in the substantia nigra and striatum... (More)
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 Nrg1ß(1) (Nrg1ß(1) -ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1ß(1) -ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1ß(1) -ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1ß(1) -ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for PD patients. (Less)
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Contribution to journal
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keywords
ErbB4 receptor, dopamine, neuregulin, neuroprotection, Parkinson's, disease
in
Journal of Neurochemistry
volume
117
issue
6
pages
1066 - 1074
publisher
Wiley-Blackwell
external identifiers
  • wos:000291223800013
  • pmid:21517849
  • scopus:79957999312
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2011.07284.x
language
English
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yes
id
2c38a59a-48e5-445d-8b8d-4e3999567bef (old id 1936748)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21517849?dopt=Abstract
date added to LUP
2011-05-02 16:14:08
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2017-09-03 03:18:14
@article{2c38a59a-48e5-445d-8b8d-4e3999567bef,
  abstract     = {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 Nrg1ß(1) (Nrg1ß(1) -ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1ß(1) -ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1ß(1) -ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1ß(1) -ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for PD patients.},
  author       = {Carlsson, Thomas and Schindler, Friederike R and Höllerhage, Matthias and Depboylu, Candan and Arias-Carrión, Oscar and Schnurrbusch, Stefan and Rösler, Thomas W and Wozny, Wojciech and Schwall, Gerhard P and Groebe, Karlfried and Oertel, Wolfgang H and Brundin, Patrik and Schrattenholz, André and Höglinger, Günter U},
  issn         = {1471-4159},
  keyword      = {ErbB4 receptor,dopamine,neuregulin,neuroprotection,Parkinson's,disease},
  language     = {eng},
  number       = {6},
  pages        = {1066--1074},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Systemic administration of Neuregulin-1ß(1) protects dopaminergic neurons in a mouse model of Parkinson's disease.},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2011.07284.x},
  volume       = {117},
  year         = {2011},
}