D(1)-like dopamine receptors regulate GABA(A) receptor function to modulate hippocampal neural progenitor cell proliferation

作者：Goffin Darren; Aarum Johan^*; Schroeder Joern E; Jovanovic Jasmina N; Chuang Tsu Tshen

来源：Journal of Neurochemistry, 2008, 107(4): 964-975.

DOI：10.1111/j.1471-4159.2008.05679.x

• calcium
• dopamine
• GABA
• neural progenitor
• neural stem
• proliferation

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(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(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(1)-like dopamine receptors had no effect on proliferation, it abrogated the suppressive effects of GABA(A) receptor activation on proliferation. The effects of D(1)-like dopamine receptors are associated with a decrease in the ability of GABA(A) receptors to increase intracellular calcium levels, and a reduction in the surface expression of GABA(A) receptors. In this way, D(1)-like dopamine receptor activation can increase the proliferation of NP cells by preventing GABA(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(1)-like dopamine receptors may increase the proliferation of neural progenitors.

• 出版日期2008-11