Abstract
BackgroundThe mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson’s disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown.ResultsBy taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains.ConclusionsOur study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-729) contains supplementary material, which is available to authorized users.
Highlights
The mesencephalic dopaminergic cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells)
The study was limited to samples where 1-5 μg of total RNA could be obtained. To expand this analysis to tiny amounts of ex vivo tissue and to the polyA− fraction of RNAs, we developed nanoCAGE, a technology that miniaturizes the requirement of Cap Analysis of Gene Expression (CAGE) for RNA material to the nanogram range and which can be used on fixed tissues [12]
Identification of Olfactory Receptors (OR) transcripts by expression analysis of mesencephalic dopaminergic (mDA) neurons We have determined the gene expression profiles of mDA neurons with nanoCAGE technology. To this purpose we took advantage of transgenic mice that selectively express green fluorescent protein (GFP) in catecholaminergic cells under the control of tyrosine hydroxylase (TH) gene promoter (TH-GFP mice) [14]. In this mouse line we can identify the majority of mDA neurons for their GFP labeling
Summary
The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson’s disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. Mesencephalic dopaminergic neurons (mDA) are the major source of dopamine in the brain They present two major groups of projecting cells: the A9 neurons of the Substantia Nigra (SN) that form the mesostriatal system and the A10 cells of the Ventral. Selective degeneration of A9 cells leads to Parkinson’s Disease (PD) [3], while altered function of A10 cells has been linked to schizophrenia, attention deficit disorder and addiction [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
