Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

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

In English

Författare

  • Candan Depboylu
  • Matthias Hoellerhage
  • Stefan Schnurrbusch
  • Patrik Brundin
  • Wolfgang H. Oertel
  • Andre Schrattenholz
  • Gunter U. Hoeglinger

Summary, in English

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.

Publiceringsår

2012

Språk

Engelska

Sidor

209-214

Publikation/Tidskrift/Serie

Neuroscience Letters

Volym

531

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Neurosciences

Nyckelord

  • ErbB4
  • Neuregulin
  • Dopamine
  • Parkinson
  • Neurodegeneration

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0304-3940