Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons
Article first published online: 1 APR 2005
Journal of Neurochemistry
Volume 93, Issue 4, pages 974–983, May 2005
How to Cite
Iwakura, Y., Piao, Y.-s., Mizuno, M., Takei, N., Kakita, A., Takahashi, H. and Nawa, H. (2005), Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons. Journal of Neurochemistry, 93: 974–983. doi: 10.1111/j.1471-4159.2005.03073.x
- Issue published online: 22 APR 2005
- Article first published online: 1 APR 2005
- Received September 1, 2004; revised manuscript received January 4, 2005; accepted January 5, 2005.
- epidermal growth factor;
- Parkinson's disease;
- post-mortem brain;
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.