Present address: Department of Molecular Neurobiology, The Salk Institute for Biological Sciences, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
MPTP selectively induces haem oxygenase-1 expression in striatal astrocytes
Article first published online: 24 DEC 2001
European Journal of Neuroscience
Volume 12, Issue 5, pages 1573–1583, May 2000
How to Cite
Fernandez-Gonzalez, A., Pérez-Otaño, I. and Morgan, J. I. (2000), MPTP selectively induces haem oxygenase-1 expression in striatal astrocytes. European Journal of Neuroscience, 12: 1573–1583. doi: 10.1046/j.1460-9568.2000.00044.x
- Issue published online: 24 DEC 2001
- Article first published online: 24 DEC 2001
- Received 23 August 1999, revised 9 December 1999, accepted 28 January 2000
- haem metabolism;
- tyrosine hydroxylase
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta with accompanying evidence of increased oxidative damage, deficits in mitochondrial function and iron deposition. Recently, haem oxygenase-1 levels were reported to be elevated in PD brains. Because this enzyme is involved in the response to oxidative stress and is critical for cellular haem and iron homeostasis, it could play a role in the pathogenesis of PD. Therefore, we investigated the expression of haem oxygenase isoform 1 (HO-1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP triggered a relatively rapid and persistent increase in HO-1 mRNA exclusively in the mouse striatum. In situ hybridization and immunohistochemistry showed HO-1 to be localized to striatal astrocytes. The induction of HO-1 by MPTP was blocked by selegiline and GBR-12909, indicating the protoxin had to be metabolized by monoamine oxidase B and taken up by dopaminergic neurons to exert its action in astrocytes. MPTP did not alter the expression of other enzymes of haem synthesis or degradation nor were the levels of mRNA for haem or iron-binding proteins changed. Thus, expression of HO-1 was not part of a cellular program involving haem biosynthesis or homeostasis. In addition, heat shock proteins were not induced by MPTP. Thus, MPTP elicited a selective transcriptional response in striatal astrocytes. This response appears to be mediated by molecules released from affected dopaminergic nerve terminals in the striatum acting upon neighbouring astrocytes. This signalling pathway and its potential relevance to PD are discussed.