Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer.
Brain-derived neurotrophic factor (BDNF) was expressed via injection of viral vector into the substantia nigra pars compacta (SNc) to investigate its influence on nigrostriatal dopaminergic activity and locomotor behavior. The recombinant adeno-associated virus (rAAV) vector, pTR-BDNFmyc, incorporated the neuron-specific enolase (NSE) promoter and the internal ribosome entry site (IRES) element driving expression of both epitope-tagged BDNF and green fluorescent protein (GFP) bicistronically. The control vector, pTR-UF4, incorporated NSE promoter-driven GFP expression only. Transgene expression persisted in both vector groups throughout the 9 month course of the study. Partial 6-hydroxydopamine (6-OHDA) lesions were conducted in the SNc ipsilateral to, and 6 months after, transduction with either the pTR-BDNFmyc or the pTR-UF4. Transgenic BDNFmyc had no effect on the number of tyrosine hydroxylase (TH)-labeled neurons in the SNc after 6-OHDA-lesions, but did block the amphetamine-induced, ipsiversive, turning-behavior caused by the lesion in the pTR-UF4 group. The BDNFmyc-transduced group also demonstrated more locomotor activity and rotational activity contralateral to the lesioned side than did the pTR-UF4-transduced group. Long-term, stable expression of BDNF can therefore modulate locomotor activity without significantly affecting nigrostriatal dopaminergic survival.
Klein
R L
RL
Department of Pharmacology and Therapeutics, University of Florida, Campus Box 100267 JHMHC, Gainesville, FL 32610, USA.
Lewis
M H
MH
Muzyczka
N
N
Meyer
E M
EM
D018663:Adrenergic Agents; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009043:Motor Activity / Q000235:genetics*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D018663:Adrenergic Agents; D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D016627:Oxidopamine; D000661:Amphetamine