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Systemic administra...
Systemic administration of Neuregulin-1ß(1) protects dopaminergic neurons in a mouse model of Parkinson's disease.
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Carlsson, Thomas (author)
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Schindler, Friederike R (author)
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Höllerhage, Matthias (author)
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Depboylu, Candan (author)
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Arias-Carrión, Oscar (author)
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Schnurrbusch, Stefan (author)
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Rösler, Thomas W (author)
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Wozny, Wojciech (author)
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Schwall, Gerhard P (author)
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Groebe, Karlfried (author)
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Oertel, Wolfgang H (author)
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- Brundin, Patrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Schrattenholz, André (author)
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Höglinger, Günter U (author)
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(creator_code:org_t)
- 2011-05-13
- 2011
- English.
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In: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 117:6, s. 1066-1074
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- ErbB4 receptor
- dopamine
- neuregulin
- neuroprotection
- Parkinson's
- disease
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Carlsson, Thomas
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Schindler, Fried ...
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Höllerhage, Matt ...
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Depboylu, Candan
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Arias-Carrión, O ...
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Schnurrbusch, St ...
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show more...
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Rösler, Thomas W
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Wozny, Wojciech
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Schwall, Gerhard ...
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Groebe, Karlfrie ...
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Oertel, Wolfgang ...
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Brundin, Patrik
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Schrattenholz, A ...
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Höglinger, Günte ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Journal of Neuro ...
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Lund University