In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin

The glial cell line-derived neurotrophic factor (GDNF)-family of neurotroph ic factors consisted until recently of three members, GDNF, neurturin, and persephin. We describe here the cloning of a new GDNF-family member, neubla stin (NBN), identical to artemin (ART), recently published (Baloh et al., 1 998). Addition of NBN/ART to cultures of fetal mesencephalic dopamine (DA) neurons increased the number of surviving tyrosine hydroxylase (TH)-immunor eactive neurons by similar to 70%, similar to the maximal effect obtained w ith GDNF. To investigate the neuroprotective effects in vivo, lentiviral ve ctors carrying the cDNA for NBN/ART or GDNF were injected into the striatum and Ventral midbrain. Three weeks after an intrastriatal 6-hydroxydopamine lesion only about 20% of the nigral DA neurons were left in the control gr oup, while 80-90% of the DA neurons remained in the NBN/ART and GDNF treatm ent groups, and the striatal TH-immunoreactive innervation was partly spare d. We conclude that NBN/ART, similarly to GDNF, is a potent neuroprotective factor for the nigrostriatal DA neurons in vivo.