ELEVATION OF NEURONAL MAO-B ACTIVITY IN A TRANSGENIC MOUSE MODEL DOESNOT 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 do paminergic neurons to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP), 8-week-old transgenic mice expressing high neurona l levels of MAO-B were compared with age-matched nontransgenic litterm ates following i.p. injections of 30 mg/kg body weight of the protoxin . Levels of striatal dopamine (DA) and its metabolite 3,4-dihydroxyphe nylacetic acid (DOPAC), as well as tyrosine hydroxylase (TH)-immunopos itive cell numbers in the substantia nigra (SN) were compared 1 week l ater between transgenics and controls. No difference was found in any of these parameters, indicating that high neuronal MAO-B levels does n ot cause increased sensitivity to MPTP, and therefore neither conversi on of MPTP to its active form, 1-methyl-4-phenyl pyridium (MPP +) by M AO-B nor MPP + uptake by the dopaminergic transporter are likely to be the rate-limiting step in the toxicity of this compound.