Alterations in m-RNA expression for Cu,Zn-superoxide dismutase and glutathione peroxidase in the basal ganglia of MPTP-treated marmosets and patients with Parkinson’s disease

Abstract

Alterations occurring in the antioxidant enzymes, copper, zinc-dependent superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPX) following nigral dopaminergic denervation are unclear. We now report on the distribution and levels of m-RNA for Cu,Zn-SOD and GPX in basal ganglia of normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, and in normal individuals and patients with Parkinson’s disease (PD) using in situ hybridization histochemistry and oligodeoxynucleotide (single-stranded DNA) probes. Cu,Zn-SOD and GPX m-RNA was present throughout basal ganglia (nucleus accumbens, caudate-putamen, globus pallidus, substantia nigra) in the common marmoset, with the highest levels being in substantia nigra (SN). Following MPTP induced nigral cell loss, Cu,Zn-SOD m-RNA levels were decreased in all areas but the SNr, and particularly in SNc (71%, P<0.001). MPTP-treatment had no effect on GPX m-RNA expression in any area of basal ganglia. Cu,Zn-SOD and GPX m-RNA was also present in the normal human SN. In PD, however, Cu,Zn-SOD m-RNA was significantly decreased (89%, P<0.005) in SNc, and there was a near-complete loss of GPX m-RNA in both SNc (100%, P<0.005) and SNr (88%, P<0.005). The loss of Cu,Zn-SOD m-RNA in SNc in MPTP-treated marmosets and patients with PD suggests that it is primarily located in dopaminergic neuronal cell bodies. The loss of GPX m-RNA in SNc in PD also suggests a localisation to dopaminergic cell bodies, but the similar change in SNr may indicate its presence in dopaminergic neurites. In contrast, the absence of change in GPX m-RNA in MPTP-treated primates appears to rule out its presence in dopaminergic cells in this species, but this may only be apparent and may reflect increased expression in glial cells following acute toxin treatment.