Yuta Ishizuka
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Pathophysiology and Metabolism,
   Position   Assistant Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Qualitative and quantitative re-evaluation of epidermal growth factor-ErbB1 action on developing midbrain dopaminergic neurons in vivo and in vitro: target-derived neurotrophic signaling (Part 1).
Journal Formal name:Journal of neurochemistry
Abbreviation:J Neurochem
ISSN code:14714159/00223042
Domestic / ForeginForegin
Publisher WILEY
Volume, Issue, Page 118(1),pp.45-56
Author and coauthor Yuriko Iwakura, Yingjun Zheng, Maria Sibilia, Yuichi Abe, Ying-Shan Piao, Daisaku Yokomaku, Ran Wang, Yuta Ishizuka, Nobuyuki Takei, Hiroyuki Nawa*
Publication date 2011/07
Summary Although epidermal growth factor (EGF) receptor (ErbB1) is implicated in Parkinson's disease and schizophrenia, the neurotrophic action of ErbB1 ligands on nigral dopaminergic neurons remains controversial. Here, we ascertained colocalization of ErbB1 and tyrosine hydroxylase (TH) immunoreactivity and then characterized the neurotrophic effects of ErbB1 ligands on this cell population. In mesencephalic culture, EGF and glial-derived neurotrophic factor (GDNF) similarly promoted survival and neurite elongation of dopaminergic neurons and dopamine uptake. The EGF-promoted dopamine uptake was not inhibited by GDNF-neutralizing antibody or TrkB-Fc, whereas EGF-neutralizing antibody fully blocked the neurotrophic activity of the conditioned medium that was prepared from EGF-stimulated mesencephalic cultures. The neurotrophic action of EGF was abolished by ErbB1 inhibitors and genetic disruption of erbB1 in culture. In vivo administration of ErbB1 inhibitors to rat neonates diminished TH and dopamine transporter (DAT) levels in the striatum and globus pallidus but not in the frontal cortex. In parallel, there was a reduction in the density of dopaminergic varicosities exhibiting intense TH immunoreactivity. In agreement, postnatal erbB1-deficient mice exhibited similar decreases in TH levels. Although neurotrophic supports to dopaminergic neurons are redundant, these results confirm that ErbB1 ligands contribute to the phenotypic and functional development of nigral dopaminergic neurons.
DOI 10.1111/j.1471-4159.2011.07287.x
PMID 21517852