Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain dopaminergic neurons in Parkinson disease.
Neurosci Lett
; 531(2): 209-14, 2012 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-23123776
ABSTRACT
Previously we demonstrated that systemically administered neuregulin-1-ß1, 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-ß1 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Mesencéfalo
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Neurônios Dopaminérgicos
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Receptores ErbB
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha