Aged Tgfbeta2/Gdnf double-heterozygous mice show no morphological and functional alterations in the nigrostriatal system.

Loss of dopaminergic neurons in the substantia nigra pars compacta and the resulting decrease in striatal dopamine levels are the hallmarks of Parkinson's disease. Tgfbeta and Gdnf have been identified as neurotrophic factors for dopaminergic midbrain neurons in vivo and in vitro. Haploinsufficiency for either Tgfbeta or Gdnf led to dopaminergic deficits. In this study we therefore analyzed the nigrostriatal system of aged Tgfbeta2 (+/-)/Gdnf (+/-) double-heterozygous mice. Unexpectedly, we found no morphological changes in the nigrostriatal system as compared with age-matched wild-type mice. There were no significant differences in the number of TH-positive midbrain neurons and no changes in the optical density of TH immunoreactivity in striata of Tgfbeta2 (+/-)/Gdnf (+/-) double-heterozygous mice. Moreover, we found no significant differences in the striatal levels of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid. Our results indicate that a combined haploinsufficiency for Tgfbeta2 and Gdnf has no impact on the function and the survival of midbrain DA neurons under normal aging conditions.