6-Hydroxydopamine-lesioning of the nigrostriatal pathway in rats alters basal ganglia mRNA for copper, zinc- and manganese-superoxide dismutase, but not glutathione peroxidase.
The effects of nigrostriatal pathway destruction on the mRNA levels of copper, zinc-dependent superoxide dismutase (Cu,Zn-SOD), manganese-dependent superoxide dismutase (Mn-SOD), and glutathione peroxidase in basal ganglia of adult rat were investigated using in situ hybridization histochemistry and oligodeoxynucleotide (single-stranded complementary DNA) probes. The 6-hydroxydopamine (6-OHDA)-induced destruction of the nigrostriatal pathway resulted in contralateral rotation to apomorphine and a marked loss of specific [(3)H]mazindol binding in the striatum (93%; P<0.05) and of tyrosine hydroxylase mRNA in substantia nigra pars compacta (SC) (93%; P<0.05) compared with control rats. Levels of Cu,Zn-SOD mRNA were decreased in the striatum, globus pallidus, and SC on the lesioned side of 6-OHDA-lesioned rats compared with sham-lesioned rats (P<0.05). Levels of Mn-SOD mRNA were increased in the nucleus accumbens (P<0.05), but decreased in the SC (P<0.05) on the lesioned side of 6-OHDA-treated rats compared with sham-lesioned rats. Lesioning with 6-OHDA had no effect on glutathione peroxidase mRNA levels in any region of basal ganglia examined. The significant changes in Cu,Zn-SOD and Mn-SOD mRNA indicate that SOD is primarily expressed by dopaminergic neurons of the nigrostriatal pathway, and that the Mn-SOD gene appears to be inducible in rat basal ganglia in response to both physical and chemical damage 5 weeks after 6-OHDA-lesioning. These findings may clarify the status of antioxidant enzymes, particularly Mn-SOD, in patients with Parkinson's disease and their relevance to disease pathogenesis.
Kunikowska
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G
Neurodegenerative Diseases Research Centre, Division of Pharmacology and Therapeutics, Guy's, King's and St Thomas' School of Biomedical Sciences, Hodgkin Building, King's College, London SE1 1UL, UK.
Jenner
P
P
D018759:Adrenergic Uptake Inhibitors / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D015342:DNA Probes; D004298:Dopamine / Q000502:physiology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D008454:Mazindol / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013565:Sympatholytics
D018759:Adrenergic Uptake Inhibitors; D015342:DNA Probes; D012333:RNA, Messenger; D013565:Sympatholytics; D016627:Oxidopamine; D008454:Mazindol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D004298:Dopamine