Midbrain dopaminergic neuronal degeneration in a transgenic mouse model of familial amyotrophic lateral sclerosis

摘要: Familial amyotrophic lateral sclerosis has been linked in 15% of families to mutations the gene encoding for copper-zinc superoxide dismutase (Cu/Zn-SOD), a key enzyme cellular defense mechanisms against free radical attack. We used transgenic mouse model familial (transgenic G1H mice) based on expression mutant human Cu/Zn-SOD examine influence transgene midbrain dopaminergic neurons, cells that contain conspicuous amounts this enzyme. At time 50% motor neurons spinal cord were lost, we observed concurrent reductions dopamine levels caudate-putamen and nucleus accumbens mice. In addition, numbers tyrosine hydroxylase-immunostained significantly reduced both substantia nigra (26%) ventral tegmental area (16%) compared those their nontransgenic littermates. Similar abnormalities not brains mice overexpressing wild-type Cu/Zn-SOD. These findings indicate overexpression mutated protein caused significant loss addition neurons. The potential induce cell death extending beyond is consistent with description degeneration some patients sclerosis. Furthermore, if conclusively shown kill by oxidative stress, such an observation would be keeping known sensitivity