Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer

Brain-derived neurotrophic factor (BDNF) was expressed via injection of vir al vector into the substantia nigra pars compacta (SNc) to investigate its influence on nigrostriatal dopaminergic activity and locomotor behavior. Th e recombinant adeno-associated virus (rAAV) vector, pTR-BDNFmyc, incorporat ed the neuron-specific enolase (NSE) promoter and the internal ribosome ent ry site (IRES) element driving expression of both epitope-tagged BDNF and g reen fluorescent protein (GFP) bicistronically. The control vector, pTR-UF4 , incorporated NSE promoter-driven GFP expression only. Transgene expressio n persisted in both vector groups throughout the 9 month course of the stud y. Partial B-hydroxydopamine (6-OHDA) lesions were conducted in the SNc ips ilateral to, and 6 months after, transduction with either the pTR-BDNFmyc o r the pTR-UF4, Transgenic BDNFmyc had no effect on the number of tyrosine h ydroxylase (TH)-labeled neurons in the SNc after 6-OHDA-lesions, but did bl ock the amphetamine-induced, ipsiversive, turning-behavior caused by the le sion in the pTR-UF4 group. The BDNFmyc-transduced group also demonstrated m ore locomotor activity and rotational activity contralateral to the lesione d side than did the pTR-UF4-transduced group. Long-term, stable expression of BDNF can therefore modulate locomotor activity without significantly aff ecting nigrostriatal dopaminergic survival. (C) 1999 Elsevier Science B.V. All rights reserved.