Dopamine stimulation of postnatal murine subventricular zone neurogenesis via the D3 receptor

• Published in: Journal of neurochemistry 2010-08, Vol.114 (3), p.750-760
• Main Authors: Kim, Yongsoo, Wang, Wei-Zhi, Comte, Isabelle, Pastrana, Erika, Tran, Phuong B, Brown, Jennifer, Miller, Richard J, Doetsch, Fiona, Molnár, Zoltán, Szele, Francis G
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Astrocytes - cytology; Astrocytes - metabolism; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell growth; Cell Movement - physiology; Cell Proliferation; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine; Dopamine - metabolism; Dopamine - physiology; dopamine receptor 3; Fundamental and applied biological sciences. Psychology; Lateral Ventricles - cytology; Lateral Ventricles - growth & development; Mice; Mice, Transgenic; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Neurochemistry; neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neurons; Neurons - cytology; Neurons - metabolism; proliferation; Receptors, Dopamine D3 - genetics; Receptors, Dopamine D3 - physiology; Rodents; stem cells; Stem Cells - metabolism; Stem Cells - physiology; subventricular zone; U-99194A; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06799.x

J. Neurochem. (2010) 114, 750-760. 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.