Papers

May, 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
  • Y Iwakura
  • ,
  • YS Piao
  • ,
  • M Mizuno
  • ,
  • N Takei
  • ,
  • A Kakita
  • ,
  • H Takahashi
  • ,
  • H Nawa

Volume
93
Number
4
First page
974
Last page
983
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1111/j.1471-4159.2005.03073.x
Publisher
BLACKWELL PUBLISHING LTD

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 (TGF alpha) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGF alpha, 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 TGF alpha 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.

Link information
DOI
https://doi.org/10.1111/j.1471-4159.2005.03073.x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/15857400
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000228721200019&DestApp=WOS_CPL
ID information
  • DOI : 10.1111/j.1471-4159.2005.03073.x
  • ISSN : 0022-3042
  • Pubmed ID : 15857400
  • Web of Science ID : WOS:000228721200019

Export
BibTeX RIS