Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain dopaminergic neurons in Parkinson disease

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Depboylu, Candan (author)

Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain dopaminergic neurons in Parkinson disease

Article/chapterEnglish2012

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Elsevier BV,2012

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LIBRIS-ID:oai:lup.lub.lu.se:d84ff655-b2d2-41a5-ab0c-93e0645fec21
https://lup.lub.lu.se/record/3512169URI
https://doi.org/10.1016/j.neulet.2012.10.050DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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Previously we demonstrated that systemically administered neuregulin-1-beta 1, a nerve growth and differentiation factor, passed the blood-brain barrier and accumulated in brain areas with expression of its receptor ErbB4. In substantia nigra (SN), neuregulin-1-beta 1 phosphorylated ErbB4 and protected dopaminergic neurons in a toxin-based mouse model of Parkinson disease (PD). We studied ErbB4 in the context of human midbrain dopaminergic degeneration in vivo and in vitro. Post-mortem ventral midbrain tissue sections of neuropsychiatric healthy individuals and PD patients (matched for age, gender and post-mortem delay) were immunostained for ErbB4. Cultured Lund human mesencephalic (LUHMES) post-mitotic dopaminergic neurons were treated with dopaminergic toxins and analyzed for ErbB4 expression. In control individuals, 85.0 +/- 5.0% of dopaminergic neurons, containing cytoplasmic neuromelanin, expressed ErbB4 in the SN. In PD cases, the percentage of ErbB4-positive nigral dopaminergic neurons was increased to 94.9 +/- 2.5%. The mean ErbB4 immunoreactivity of melanized neurons was higher in PD than controls. LUHMES neurons upregulated ErbB4 when exposed to toxins 1-methyl-4-phenylpyridinium and 6-hydroxydopamine. Increased rate of ErbB4-positive dopaminergic neurons in PD may either reflect a better survival of ErbB4-positive neurons or an increased expression of ErbB4 by remaining neurons to seek trophic support. Enhanced ErbB4 expression in human in vitro toxin-based PD models supports the latter interpretation. Thus, dopaminergic neurons in SN might be susceptible to neuregulin-1 treatment in PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
ErbB4
Neuregulin
Dopamine
Parkinson
Neurodegeneration

Added entries (persons, corporate bodies, meetings, titles ...)

Hoellerhage, Matthias (author)
Schnurrbusch, Stefan (author)
Brundin, PatrikLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-pbr (author)
Oertel, Wolfgang H. (author)
Schrattenholz, Andre (author)
Hoeglinger, Gunter U. (author)
Institutionen för experimentell medicinsk vetenskapMedicinska fakulteten (creator_code:org_t)

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In:Neuroscience Letters: Elsevier BV531:2, s. 209-2140304-3940

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