Dopamine stimulation of postnatal murine subventricular zone neurogenesis via the D3 receptor.
We investigated the expression and role of the dopamine receptor 3 (D3R) in postnatal mouse subventricular zone (SVZ). In situ hybridization detected selective D3R mRNA expression in the SVZ. Fluorescence activated cell sorting (FACS) of adult SVZ subtypes using hGFAP-GFP and Dcx-GFP mice showed that transit amplifying progenitor cells and niche astrocytes expressed D3R whereas stem cell-like astrocytes and neuroblasts did not. To determine D3R's role in SVZ neurogenesis, we administered U-99194A, a D3R preferential antagonist, and bromodeoxyuridine in postnatal mice. In vivo D3R antagonism decreased the numbers of newborn neurons reaching the core and the periglomerular layer of the olfactory bulb. Moreover, it decreased progenitor cell proliferation but did not change the number of label-retaining (stem) cells, commensurate with its expression on transit amplifying progenitor cells but not SVZ stem cell-like astrocytes. Collectively, this study suggests that dopaminergic stimulation of D3R drives proliferation via rapidly amplifying progenitor cells to promote murine SVZ neurogenesis.
Kim
Yongsoo
Y
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Wang
Wei-Zhi
WZ
Comte
Isabelle
I
Pastrana
Erika
E
Tran
Phuong B
PB
Brown
Jennifer
J
Miller
Richard J
RJ
Doetsch
Fiona
F
Molnár
Zoltán
Z
Szele
Francis G
FG
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D000089662:Doublecortin Protein; D020547:Lateral Ventricles / Q000166:cytology* / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D050637:Receptors, Dopamine D3; D004298:Dopamine