Display Settings:

Format

Send to:

Choose Destination
Brain. 2008 Mar;131(Pt 3):630-41. doi: 10.1093/brain/awm340. Epub 2008 Jan 17.

Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson's disease.

Author information

  • 1Cambridge Center for Brain Repair and Department of Clinical Neurosciences, Forvie Site, Robinsons Way, Cambridge CB2 2PY, UK.

Abstract

Neural stem cells (NSCs) are widely endorsed as a cell source for replacement strategies in neurodegenerative disease. However, their usefulness is currently limited by the inability to induce specific neurotransmitter phenotypes in these cells. In order to direct dopaminergic neuronal fate, we overexpressed Pitx3 in NSCs that were then exposed to E11 developing ventral mesencephalon (VM) in explant culture. This resulted in a significant potentiation of dopaminergic differentiation of the cells. When transplanted into the 6-hydroxydopamine lesioned Parkinsonian rats, these cografts of VM and Pitx3 overexpressing NSCs resulted in a significant restitution of motor function. In addition, there were greater numbers of Girk2 positive A9 neurons in the periphery of the transplants that were NSC derived. This demonstrates that given the correct signals, NSCs can be induced to become dopaminergic neurons that can differentiate into the correct nigrastriatal phenotype required for the treatment of Parkinson's disease.

PMID:
18202103
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk