Effects of short- and long-term (--)-deprenyl administration on mRNA for copper, zinc- and manganese-superoxide dismutase and glutathione peroxidase in rat brain.
The effect of short-term (3 weeks, 2 mg/kg day) and long-term (12 and 20 months, 0.5 mg/kg day) administration of (-)-deprenyl on the mRNA expression of three neuroprotective enzymes in subdivisions of rat basal ganglia was investigated. In situ hybridisation histochemistry with oligodeoxynucleotide probes was used to measure levels of copper, zinc superoxide dismutase (Cu,Zn-SOD), manganese superoxide dismutase (Mn-SOD), and glutathione peroxidase (GPX) mRNA. The 3-week administration of (-)-deprenyl caused a significant increase in Cu,Zn-SOD mRNA in the nucleus accumbens (NA) (P<0.05), striatum (CP) (P<0.01), and globus pallidus (GP) (P<0.05), but had no effect on Mn-SOD or GPX mRNA levels throughout basal ganglia. In rats which received (-)-deprenyl for 12 months, there was a significant increase in Mn-SOD mRNA in the NA, CP, GP, and substantia nigra (SN) (all P<0.05); there were no changes in either Cu,Zn-SOD or GPX mRNA. Except for the significant increase in Cu,Zn-SOD mRNA in SN pars compacta (SC) (P<0.05), by 20 months there were almost no differences between (-)-deprenyl-treated and age-matched control animals that had received equivalent injections of saline. We conclude that (-)-deprenyl administration can induce mRNA expression for both forms of SOD, but the effects are variable and not sustained over 20 months.
Kunikowska
Grazyna
G
Neurodegenerative Diseases Research Centre, Division of Pharmacology & Therapeutics, Guy's, King's and St. Thomas School of Biomedical Sciences, Hodgkin Building, Guy's Campus, London SE1 1UL, UK.
Gallagher
Imelda
I
Glover
Vivette
V
Clow
Angela
A
Jenner
Peter
P
D000818:Animals; D001479:Basal Ganglia / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000235:genetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D012642:Selegiline; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase