Elevation of neuronal MAO-B activity in a transgenic mouse model does not increase sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

To examine whether expressing high levels of monoamine oxidase (MAO-B) activity abberently in neurons results in increased sensitivity of dopaminergic neurons to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 8-week-old transgenic mice expressing high neuronal levels of MAO-B were compared with age-matched nontransgenic littermates following i.p. injections of 30 mg/kg body weight of the protoxin. Levels of striatal dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), as well as tyrosine hydroxylase (TH)-immunopositive cell numbers in the substantia nigra (SN) were compared 1 week later between transgenics and controls. No difference was found in any of these parameters, indicating that high neuronal MAO-B levels does not cause increased sensitivity to MPTP, and therefore neither conversion of MPTP to its active form, 1-methyl-4-phenyl pyridium (MPP+) by MAO-B nor MPP+ uptake by the dopaminergic transporter are likely to be the rate-limiting step in the toxicity of this compound.