title: Vascular endothelial growth factor-B is neuroprotective in an in vivo rat model of Parkinson's disease.
abstract: Developing novel neuroprotective strategies for the treatment of Parkinson's disease (PD) is of great importance. We have previously shown that vascular endothelial growth factor-B (VEGF-B) is up-regulated in an in vitro model of PD using the neurotoxin rotenone. Addition of exogenous VEGF-B(167) was neuroprotective in this same model, suggesting that VEGF-B is a natural response to neurodegenerative challenges. Now we have extended this research using in vivo experiments. We tested a single intra-striatal injection of 3 μg VEGF-B(186), the more diffusible VEGF-B isoform, in a mild progressive unilateral 6-hydroxydopamine (6-OHDA) rat in vivo PD model. Treatment with VEGF-B(186) 6h prior to lesioning with 6-OHDA improved amphetamine-induced rotations and forepaw preference at 2, 4 and 6 weeks post-injection, indicating a neuroprotective effect. Immunohistochemical analysis showed that VEGF-B(186) treatment partially protected dopaminergic fibers in the striatum and demonstrated a partial rescue of the dopaminergic neurons in the caudal sub-region of the substantia nigra. Altogether our data suggest that VEGF-B(186) could be a new candidate trophic factor for the treatment of PD.
authors.affiliation: Department of Neurology, College of Medicine, The University of Arizona, Tucson, AZ 85724, United States. tfalk@u.arizona.edu
authors.forename: Torsten
authors.initials: T
authors.lastname: Falk
authors.forename: Xu
authors.initials: X
authors.lastname: Yue
authors.forename: Shiling
authors.initials: S
authors.lastname: Zhang
authors.forename: Alexander D
authors.initials: AD
authors.lastname: McCourt
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Yee
authors.forename: Robert T
authors.initials: RT
authors.lastname: Gonzalez
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Sherman
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001526:Behavioral Symptoms / Q000209:etiology / Q000517:prevention & control*; D002452:Cell Count; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects; D009410:Nerve Degeneration / Q000209:etiology* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000209:etiology / Q000473:pathology; D010455:Peptides / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D010455:Peptides; C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase