Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules

BMC Genomics

Stefano Gustincich⁶  Piero Carninci⁸  the FANTOM Consortium  Charles Plessy⁸  Claudia Lodovichi⁵  Isidro Ferrer⁴  Paolo Carloni⁷  Yoshihide Hayashizaki⁸  Alistair RR Forrest⁸  Francesca Persichetti⁹  Roberto Simone^1,10  Christina Vlachouli^1,10  Paula Garcia-Esparcia⁴  Alejandro Giorgetti³  Paola Roncaglia²  Giovanni Pascarella⁸  Dejan Lazarevic¹  Ilaria Zamparo⁵  Alice Urzì^1,10  Silvia Zucchelli⁹  Alice Grison^1,10 

[1] CBM, AREA Science Park, s.s. 14, Km 163.5, Basovizza 34012 Trieste, Italy;Current address: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hixton, Cambridge CB10 1SD, UK;Department of Biotechnology, University of Verona, Ca’ Vignal 1, Strada Le Grazie 15, 37134 Verona, Italy;Institute of Neuropathology, IDIBELL-University Hospital of Bellvitge, Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain;Venetian Institute of Molecular Medicine (VIMM), via Orus 2, 35129 Padua, Italy;The Giovanni Armenise-Harvard Foundation Laboratory, SISSA, via Bonomea 265, 34136 Trieste, Italy;Computational Biophysics, German Research School for Simulation Sciences (Joint venture of RWTH Aachen University and Forschungszentrum Jülich), Jülich, Germany;RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan;Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, via Solaroli 17, 28100 Novara, Italy;SISSA, Area of Neuroscience, via Bonomea 265, 34136 Trieste, Italy

关键词: Ventral midbrain;    Dopaminergic neurons;    Odorant receptors;    Odors;    NanoCAGE;   

Others  :  1141184
DOI  :  10.1186/1471-2164-15-729

 received in 2013-12-12, accepted in 2014-08-18,  发布年份 2014

【 摘 要 】

Background

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. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown.

Results

By 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.

Conclusions

Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.

【 授权许可】

   
2014 Grison et al.; licensee BioMed Central Ltd.

【 图 表 】

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