Unexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells

doi:10.1073/pnas.0813216106

Unexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells

^aSector of Neurobiology, International School for Advanced Studies,
^bThe Giovanni Armenise–Harvard Foundation Laboratory, and
^dConsorzio per il Centro di Biomedicina Molecolare, AREA Science Park, Basovizza, 34012 Trieste, Italy;
^cCentro Interdipartimentale Medicina Rigenerativa, University of Udine, 33100 Udine, Italy;
^eRIKEN Omics Science Center, Yokohama Institute 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa 230-0045, Japan;
^fDepartment of Molecular Genetics, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan;
^gCenter for Neuroscience Research, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010;
^hDepartment of Medical Sciences, University of Eastern Piedmont, 28100 Novara, Italy;
ⁱInstitute of Neuropathology, Institut d'Investigació Biomèdica de Bellvitge–University Hospital Bellvitge, University of Barcelona, 08907 Llobregat, Spain;
^jDepartment of Pediatric Hematology–Oncology, Weill Medical College of Cornell University, 515 East 71st Street, New York, NY 10021; and
^kDepartment of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115

Edited by Emilio Bizzi, Massachusetts Institute of Technology, Cambridge, MA, and approved July 6, 2009
↵¹M.B. and M.P. contributed equally to this work. (received for review December 26, 2008)

Abstract

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). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson's disease. Here, we report that gene expression analysis of A9 dopaminergic neurons (DA) identifies transcripts for α- and β-chains of hemoglobin (Hb). Globin immunoreactivity decorates the majority of A9 DA, a subpopulation of cortical and hippocampal astrocytes and mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains and in rat and human. We show that Hb is expressed in the SN of human postmortem brain. By microarray analysis of dopaminergic cell lines overexpressing α- and β-globin chains, changes in genes involved in O₂ homeostasis and oxidative phopshorylation were observed, linking Hb expression to mitochondrial function. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain and neurodegenerative diseases.

Footnotes

²To whom correspondence should be addressed. E-mail: gustinci{at}sissa.it
Author contributions: M.B., M.P., E.R., and S.G. designed research; M.B., M.P., D.C., M.Z., D.L., R.S., C.V., and C.P. performed research; A.B., K.K., V.G., C.S., I.F., S.R., C.A.B., and P.C. contributed new reagents/analytic tools; M.B., M.P., D.C., D.L., P.R., R.S., C.V., C.P., N.B., S.R., C.A.B., P.C., and S.G. analyzed data; and M.B. and S.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE16192).
This article contains supporting information online at www.pnas.org/cgi/content/full/0813216106/DCSupplemental.