Restorative effects of platelet derived growth factor-BB in rodent models of Parkinson's disease

J Parkinsons Dis. 2011;1(1):49-63. doi: 10.3233/JPD-2011-0003.

Abstract

Parkinson's disease is characterized by motor deficits caused by loss of midbrain dopaminergic neurons. Neurotrophic factors and cell transplantation have partially restored function in models of Parkinson's disease, but have had limited effects in humans. Here we show that intracerebroventricular administration of platelet-derived growth factor-BB can offer an alternative strategy to restore function in Parkinson's disease; In animal models of nigrostriatal injury, a two weeks treatment with platelet-derived growth factor-BB resulted in long-lasting restoration of striatal dopamine transporter binding sites and expression of nigral tyrosine hydroxylase. It also normalized amphetamine-induced rotational behavior in 6-hydroxydopamine lesioned rats. Platelet-derived growth factor-BB promoted proliferation of neural progenitor cells in the subventricular zone. The effects on dopaminergic neurons and functional recovery could be blocked by co-infusion with a proliferation inhibitor, indicating a link between the proliferative and anti-parkinsonian effects. Based on the current data, we consider platelet-derived growth factor-BB a clinical candidate drug for treatment of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • Angiogenesis Inducing Agents / therapeutic use*
  • Animals
  • Becaplermin
  • Cell Proliferation / drug effects
  • Cytarabine / therapeutic use
  • Disease Models, Animal
  • Drug Administration Schedule
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neurotoxins / toxicity
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Parkinson Disease / pathology
  • Proto-Oncogene Proteins c-sis / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Angiogenesis Inducing Agents
  • Immunosuppressive Agents
  • Neurotoxins
  • Proto-Oncogene Proteins c-sis
  • Cytarabine
  • Becaplermin
  • Oxidopamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine