Aged Tgf beta 2/Gdnf double-heterozygous mice show no morphological and functional alterations in the nigrostriatal system

Abstract

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. Tgf beta and Gdnf have been identified as neurotrophic factors for dopaminergic midbrain neurons in vivo and in vitro. Haploinsufficiency for either Tgf beta or Gdnf led to dopaminergic deficits. In this study we therefore analyzed the nigrostriatal system of aged Tgf beta 2 (+/-)/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 Tgf beta 2 (+/-)/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 Tgf beta 2 and Gdnf has no impact on the function and the survival of midbrain DA neurons under normal aging conditions.