イシヅカ　ユウタ   Yuta Ishizuka   石塚　佑太    所属   川崎医科大学  医学部 基礎医学　病態代謝学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	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).
掲載誌名	正式名：Journal of neurochemistry 略　 称：J Neurochem ISSNコード：14714159/00223042
掲載区分	国外
出版社	WILEY
巻・号・頁	118(1),pp.45-56
著者・共著者	Yuriko Iwakura, Yingjun Zheng, Maria Sibilia, Yuichi Abe, Ying-Shan Piao, Daisaku Yokomaku, Ran Wang, Yuta Ishizuka, Nobuyuki Takei, Hiroyuki Nawa
発行年月	2011/07
概要	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