AUTHOR=Bayer Andersen Kirsten , Leander Johansen Jens , Hentzer Morten , Smith Garrick Paul , Dietz Gunnar P. H. 

TITLE=Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP+ and Rotenone Toxicity

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 10 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00164

DOI=10.3389/fncel.2016.00164

ISSN=1662-5102

ABSTRACT=The G-protein coupled receptor 139 (GPR139) is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. Here, we examined the potential neuroprotective effect of GPR139 agonism in primary culture models of dopaminergic neuronal degeneration. We find that in vitro GPR139 agonists protected primary mesencephalic dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP+)-mediated degeneration. Protection was concentration-dependent and could be blocked by a GPR-139 antagonist. However, the protection of dopaminergic neurons was not found against rotenone or 6-hydroxydopamine (6-OHDA) mediated degeneration. Our results support differential mechanisms of toxicity for those substances commonly used in Parkinson’s disease models and potential for GPR139 agonists in neuroprotection.