Effect of MPTP on Dopamine metabolism in Ames dwarf mice.
Hypopituitary dwarf mice exhibit a heightened antioxidative capacity and live extensively longer than age-matched controls. Importantly, dwarf mice resist peripheral oxidative stress induced by paraquat, and behaviorally, they maintain cognitive function and locomotor activity at levels above those observed in old wild-type animals. We assessed monoaminergic neurotransmitters in nigrostriatal tract and cerebellum after the administration of the dopaminergic neurotoxin, MPTP. There was no significant change in mitochondrial monoamine oxidase (MAO)-B and total MAO activity in the substantia nigra and nucleus caudatus putamen of wild-type and dwarf mice. Coenzymes Q-9 and Q-10 were present in similar quantities, as were dopamine, norepinephrine, and serotonin levels in the cerebellum and nigrostriatal tract. MPTP set off tremor, hind limb abduction, and straub tail behavior and induced significant dopamine depletion in the striatum of both dwarf and normal mice. This study shows that the MAO activity and the coenzyme content of dwarf mice are similar to those of their wild-type controls and hence susceptible to MPTP-induced toxicity.
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USA.
Dhanasekaran
D
Muralikrishnan
Manuchair
M
Ebadi
Holly M
HM
Brown-Borg
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003067:Coenzymes; D004298:Dopamine / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008995:Monoamine Oxidase / Q000378:metabolism; D018384:Oxidative Stress; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D003067:Coenzymes; D014451:Ubiquinone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; C024989:coenzyme Q10; C030571:ubiquinone 9; D004298:Dopamine