PMID- 10575102 OWN - NLM STAT- MEDLINE DCOM- 19991221 LR - 20220223 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 847 IP - 2 DP - 1999 Nov 20 TI - Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. PG - 314-20 AB - 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. FAU - Klein, R L AU - Klein RL AD - Department of Pharmacology and Therapeutics, University of Florida, Campus Box 100267 JHMHC, Gainesville, FL 32610, USA. FAU - Lewis, M H AU - Lewis MH FAU - Muzyczka, N AU - Muzyczka N FAU - Meyer, E M AU - Meyer EM LA - eng GR - GM 35723/GM/NIGMS NIH HHS/United States GR - HL 53665/HL/NHLBI NIH HHS/United States GR - HL/DK 50257/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Adrenergic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Central Nervous System Stimulants) RN - 8HW4YBZ748 (Oxidopamine) RN - CK833KGX7E (Amphetamine) SB - IM MH - Adrenergic Agents MH - Amphetamine/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Central Nervous System Stimulants/pharmacology MH - *Gene Transfer Techniques MH - Genetic Vectors/genetics MH - Humans MH - Motor Activity/*genetics MH - Oxidopamine MH - Parkinson Disease/therapy MH - Rats MH - Rats, Sprague-Dawley MH - Substantia Nigra/drug effects/*metabolism EDAT- 1999/11/27 00:00 MHDA- 1999/11/27 00:01 CRDT- 1999/11/27 00:00 PHST- 1999/11/27 00:00 [pubmed] PHST- 1999/11/27 00:01 [medline] PHST- 1999/11/27 00:00 [entrez] AID - S0006-8993(99)02116-2 [pii] AID - 10.1016/s0006-8993(99)02116-2 [doi] PST - ppublish SO - Brain Res. 1999 Nov 20;847(2):314-20. doi: 10.1016/s0006-8993(99)02116-2.