부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1471-4159.2008.05679.x Byline: Darren Goffin (,,1), Johan Aarum (,1), Jorn E. Schroeder (,1), Jasmina N. Jovanovic ([dagger]), Tsu Tshen Chuang (*) Keywords: calcium; dopamine; GABA; neural progenitor; neural stem; proliferation Abstract: Abstract The proliferation and differentiation of neural progenitor (NP) cells can be regulated by neurotransmitters including GABA and dopamine. The present study aimed to examine how these two neurotransmitter systems interact to affect post-natal hippocampal NP cell proliferation in vitro. Mouse hippocampal NP cells express functional GABA.sub.A receptors, which upon activation led to an increase in intracellular calcium levels via the opening of L-type calcium channels. Activation of these GABA.sub.A receptors also caused a significant decrease in proliferation; an effect that required the entry of calcium through L-type calcium channels. Furthermore, while activation of D.sub.1-like dopamine receptors had no effect on proliferation, it abrogated the suppressive effects of GABA.sub.A receptor activation on proliferation. The effects of D.sub.1-like dopamine receptors are associated with a decrease in the ability of GABA.sub.A receptors to increase intracellular calcium levels, and a reduction in the surface expression of GABA.sub.A receptors. In this way, D.sub.1-like dopamine receptor activation can increase the proliferation of NP cells by preventing GABA.sub.A receptor-mediated inhibition of proliferation. These results suggest that, in conditions where NP cell proliferation is under the tonic suppression of GABA, agonists which act through D.sub.1-like dopamine receptors may increase the proliferation of neural progenitors. Author Affiliation: (*)Department of Neurodegeneration Research, Neurology CEDD, GlaxoSmithKline, Essex, UK ([dagger])Department of Pharmacology, The School of Pharmacy, University of London, London, UK Article History: Received April 13, 2008; revised manuscript received August 20, 2008; accepted August 21, 2008. Article note: Address correspondence and reprint requests to Tsu Tshen Chuang, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. E-mail: aaron_t_chuang@gsk.com