Promoting action of endogenous and exogenous epidermal growth factor-ErbB1 signals on the development of midbrain dopaminergic neurons

Abstract

Epidermal growth factor (EGF) binds to ErbB1 receptor and exerts a neurotrophic activity on midbrain dopaminergic neurons. Here, using EGF administrated animals and midbrain cultures, we investigated endogenous and exogenous ErbB1 activity on the development of dopaminergic neurons. Immunostaining of tyrosine hydroxylase (TH) revealed that the chronic administration of ErbB1 inhibitors (PD153035, ZD1839) to rat neonates prevented dopaminergic neurons from axonal fiber outgrowth and striatal innervation. Further, protein levels of TH and dopamine transporter decreased in the striatum but did not change in the frontal cortex. In midbrain culture, EGF had promoting activities in cell-survival and dopamine uptake. To monitor the development of intrinsic excitability of the dopaminergic neurons we prepared midbrain cultures from TH-EGFP transgenic mice. Whole-cell current-clamp recording from EGFP positive dopaminergic cells revealed that chronic treatment with EGF increased the number of action potentials induced by current injections. Further, daily administrations of EGF in vivo increased AMPA-mediated synaptic responses in the dopaminergic neurons. These findings suggest that ErbB1 ligands such as EGF have a neurotrophic activity for the development of midbrain dopaminergic neurons. [J Physiol Sci. 2006;56 Suppl:S172]