Quantitative Autoradiographic Distribution of [3H]-MPTP Binding in the Brains of Superoxide Dismutase Transgenic Mice

Recently, we have shown that transgenic mice which exhibit increased superoxide dismutase (SOD) activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Increased SOD activity has been related to impairment of cell membrane characteristics and enhanced lipid peroxidation. Thus it was thought that resistance to MPTP might possibly be attributable to alteration in the distribution of MPTP which is a highly lipophilic compound. This idea was stimulated by a previous suggestion that the resistance manifested by rats to MPTP might be due to a low level of [3H]-MPTP binding sites in brain regions which are critical to MPTP-induced toxicity. The comparison of the binding of [3H]-MPTP in the brain of SOD-transgenic mice and their nontransgenic littermates did not reveal any significant difference in either brain distribution or in concentrations of [3H]-MPTP binding between the two groups. Our data indicate that the observed lack of MPTP-induced toxicity of SOD-transgenic mice is not related to abnormal binding of the toxin in the brain of these transgenic animals which exhibit 2.07 to 3.48 higher SOD activity than their nontransgenic littermates. In addition, this study provides a normative description of the regional distribution of [3H]-MPTP binding in the brain of normal mice.