Neurotrophins prevent death and differentially affect tyrosine hydroxylase of adult rat nigrostriatal neurons in vivo.

Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) promote survival of mesencephalic dopaminergic neurons in vitro and affect normal and damaged ones in vivo. Here, these neurotrophins had markedly different potencies to prevent the death of axotomized nigrostriatal dopaminergic neurons when infused close to the rostral end of the nigral nucleus of adult rats (NT-4 > BDNF > NT-3; nerve growth factor or NGF without effect). With a high dose of BDNF (30 micrograms/day) complete protection was achieved in the rostral but not caudal nigral regions, consistent with its poor diffusion characteristics in brain tissue. Measurements of tyrosine hydroxylase immunoreactivity suggest that BDNF and NT-4 (presumably through their TrkB receptor) reduce the synthesis of this rate-limiting enzyme for dopamine synthesis in rescued as well as in normal neurons. In sharp contrast, survival-promoting doses of NT-3 (presumably through its TrkC receptor) maintained normal levels of tyrosine hydroxylase immunoreactivity in the rescued nigrostriatal neurons. These results suggest that for these adult central nervous system neurons, some neurotrophic factors are predominantly involved in facilitating cell survival, whereas others are more involved in regulating neurotransmitter function.