AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model

Exp Neurol. 2013 Oct;248:148-56. doi: 10.1016/j.expneurol.2013.06.002. Epub 2013 Jun 10.


Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with progressive pathology involving the loss of midbrain dopaminergic neurons. Neurotrophic factors are promising for PD gene therapy; they are integrally involved in the development of the nigrostriatal system. Cerebral dopamine neurotrophic factor (CDNF) was recently discovered to be more selective and potent on preserving dopaminergic neurons than other known trophic factors. The present study examined the neuroprotective and functional restorative effects of CDNF overexpression in the striatum via recombinant adeno-associated virus type 2 (AAV2.CDNF) in 6-hydroxydopamine (6-OHDA) injected rats. Striatal delivery of AAV2.CDNF was able to recover 6-OHDA-induced behavior deficits and resulted in a significant restoration of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and TH-ir fiber density in the striatum. PET analyses with [(11)C]-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ([(11)C]β-CFT) probes suggested functional recovery of dopaminergic (DA) neurons. Our results indicate that striatal administration of AAV2.CDNF was able to provide effective neuro-restoration in the 6-OHDA-lesioned nigrostriatal system and that it may be considered for future clinical applications in PD therapy.

Keywords: 6-OHDA; AAV; CDNF; PET; Parkinson's disease.

MeSH terms

  • Animals
  • Dependovirus / genetics
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / pathology
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Locomotion / drug effects
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / pathology
  • Motor Activity / drug effects
  • Nerve Growth Factors / administration & dosage
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / therapeutic use*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidopamine
  • Parkinson Disease, Secondary / drug therapy
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / therapy*
  • Rats
  • Rats, Sprague-Dawley


  • CDNF protein, human
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Oxidopamine