The Role of Dopamine D3 Receptors in the Regulation of Adult Neural Stem Cell Proliferation and Parkinson’s Disease

• Main Authors: Chu Lan Lao, 劉珠蘭
• Other Authors: J. C. Chen
• Format: Others
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/01138582102327842261

碩士 === 長庚大學 === 基礎醫學研究所 === 96 === In the adult mammalian central nervous system, neural stem cells (NSCs) persist mainly in the subventricular zone (SVZ). Dopamine D3 receptors (D3R) are abundantly expressed in the SVZ during the brain development until adulthood, thereby supports the notion that dopamine plays a role in neurogenesis during brain development. In this study, we isolated SVZ stem cells from adult wt or D3-KO mice of ages around 8-12 weeks. We demonstrate that treatment of 7-OH-DPAT or PD128907 enhances the cell proliferation in SVZ neurosphere culture as well as in transfected PC12/hD3 cell line. But, we ruled out the possibility that dopamine D2 receptors (D2R) participate in this process. Further, in in vivo study, we established a MPTP-induced Parkinson’s diseases (PD) animal model and used this model as platform to determine the possible signal transduction pathways underlying the D3R-induced cell proliferation and its impact on cell cycle. Via pharmacological manipulation, we found that striatal nestin and GFAP expression was pronounced in MPTP-treated animals, whiles both signals were even intensified after co-administration with D3R agonist, 7-OH-DPAT. In addition, we found that dopamine D1 receptors super-sensitized after MPTP treatment. The overall results implicate the administration of dopamine D3R agonist in adulthood promotes cell proliferation in the SVZ area, providing a possible cell-based therapeutic manner against neurodegenerative diseases.