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Influences of dopaminergic lesion on epidermal growth factor‐ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons
Author(s) -
Iwakura Yuriko,
Piao Yingshan,
Mizuno Makoto,
Takei Nobuyuki,
Kakita Akiyoshi,
Takahashi Hitoshi,
Nawa Hiroyuki
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03073.x
Subject(s) - dopaminergic , striatum , endocrinology , neurotrophic factors , medicine , epidermal growth factor , neurotrophin , tyrosine hydroxylase , glial cell line derived neurotrophic factor , substantia nigra , brain derived neurotrophic factor , heparin binding egf like growth factor , biology , parkinson's disease , neuroscience , dopamine , receptor , disease
Epidermal growth factor (EGF) is a member of a structurally related family containing heparin‐binding EGF‐like growth factor (HB‐EGF) and transforming growth factor alpha (TGFα) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGFα, and HB‐EGF in post‐mortem brains of patients with Parkinson's disease and age‐matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB‐EGF and TGFα levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down‐regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6‐hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease.