Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

Beate Winner; Paula Desplats; Christian Hagl; Jochen Klucken; Robert Aigner; Sonja Ploetz; Jörn Laemke; Alexandra Karl; Ludwig Aigner; Eliezer Masliah; Erich Buerger; Jürgen Winkler

doi:10.1016/j.expneurol.2009.07.013

Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

Beate Winner^*, Paula Desplats, Christian Hagl, Jochen Klucken, Robert Aigner, Sonja Ploetz, Jörn Laemke, Alexandra Karl, Ludwig Aigner, Eliezer Masliah, Erich Buerger, Jürgen Winkler

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

140 Citations (Scopus)

Abstract

Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1.0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ-derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6). Oral PPX treatment selectively increases adult neurogenesis in the SVZ-olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain.

Original language	English
Pages (from-to)	543-552
Number of pages	10
Journal	Experimental Neurology
Volume	219
Issue number	2
DOIs	https://doi.org/10.1016/j.expneurol.2009.07.013
Publication status	Published - Oct 2009
Externally published	Yes

Keywords

Adult neurogenesis
Dopamine
Dopamine agonist
Neural progenitor cells
Parkinson
Pramipexole

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10.1016/j.expneurol.2009.07.013

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@article{740adcb44eb74f12b2b8a8a32ff31f53,

title = "Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model",

abstract = "Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1.0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ-derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6). Oral PPX treatment selectively increases adult neurogenesis in the SVZ-olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain.",

keywords = "Adult neurogenesis, Dopamine, Dopamine agonist, Neural progenitor cells, Parkinson, Pramipexole",

author = "Beate Winner and Paula Desplats and Christian Hagl and Jochen Klucken and Robert Aigner and Sonja Ploetz and J{\"o}rn Laemke and Alexandra Karl and Ludwig Aigner and Eliezer Masliah and Erich Buerger and J{\"u}rgen Winkler",

note = "Funding Information: This study was supported in part by a non-restricted grant from Boehringer Ingelheim Pharma GmbH & Co. KG to J{\"u}rgen Winkler. Erich Buerger is working for B{\"o}hringer Ingelheim Pharma GmbH & Co. KG. Funding Information: This work was supported by grants from the Bavarian State Ministry of Sciences, Research and the Arts, ForNeuroCell grant (BW and JW), Boehringer Ingelheim Pharma GmbH & Co. KG (JW) and the Alexander von Humboldt Foundation (BW). The authors thank Verena May, Zacharias Kohl, Chichung D. Lie, and Fred H. Gage for helpful discussions as well as Donald P. Pizzo and Andrew Chen for excellent technical support. ",

year = "2009",

month = oct,

doi = "10.1016/j.expneurol.2009.07.013",

language = "English",

volume = "219",

pages = "543--552",

journal = "Experimental Neurology",

issn = "0014-4886",

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T1 - Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

AU - Winner, Beate

AU - Desplats, Paula

AU - Hagl, Christian

AU - Klucken, Jochen

AU - Aigner, Robert

AU - Ploetz, Sonja

AU - Laemke, Jörn

AU - Karl, Alexandra

AU - Aigner, Ludwig

AU - Masliah, Eliezer

AU - Buerger, Erich

AU - Winkler, Jürgen

N1 - Funding Information: This study was supported in part by a non-restricted grant from Boehringer Ingelheim Pharma GmbH & Co. KG to Jürgen Winkler. Erich Buerger is working for Böhringer Ingelheim Pharma GmbH & Co. KG. Funding Information: This work was supported by grants from the Bavarian State Ministry of Sciences, Research and the Arts, ForNeuroCell grant (BW and JW), Boehringer Ingelheim Pharma GmbH & Co. KG (JW) and the Alexander von Humboldt Foundation (BW). The authors thank Verena May, Zacharias Kohl, Chichung D. Lie, and Fred H. Gage for helpful discussions as well as Donald P. Pizzo and Andrew Chen for excellent technical support.

PY - 2009/10

Y1 - 2009/10

N2 - Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1.0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ-derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6). Oral PPX treatment selectively increases adult neurogenesis in the SVZ-olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain.

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KW - Adult neurogenesis

KW - Dopamine

KW - Dopamine agonist

KW - Neural progenitor cells

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ER -

Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

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