Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF

O'Keeffe Grainne, Tyers Pam, D Aarsland, Dalley Jeffrey, Barker Roger A, MA Caldwell

Research output: Contribution to journalArticle (Academic Journal)peer-review

142 Citations (Scopus)

Abstract

A reduction in dopaminergic innervation of the subventricular zone (SVZ) is responsible for the impaired proliferation of its resident precursor cells in this region in Parkinson's disease (PD). Here, we show that this effect involves EGF, but not FGF2. In particular, we demonstrate that dopamine increases the proliferation of SVZ-derived cells by releasing EGF in a PKC-dependent manner in vitro and that activation of the EGF receptor (EGFR) is required for this effect. We also show that dopamine selectively expands the GFAP(+) multipotent stem cell population in vitro by promoting their self-renewal. Furthermore, in vivo dopamine depletion leads to a decrease in precursor cell proliferation in the SVZ concomitant with a reduction in local EGF production, which is reversed through the administration of the dopamine precursor levodopa (L-DOPA). Finally, we show that EGFR(+) cells are depleted in the SVZ of human PD patients compared with age-matched controls. We have therefore demonstrated a unique role for EGF as a mediator of dopamine-induced precursor cell proliferation in the SVZ, which has potential implications for future therapies in PD
Translated title of the contributionDopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF
Original languageEnglish
Pages (from-to)8754 - 8759
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number21
DOIs
Publication statusPublished - May 2009

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