Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson's disease.
Brain
; 131(Pt 3): 630-41, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18202103
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Dopamina
/
Transplante de Tecido Encefálico
/
Transplante de Células-Tronco
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain
Ano de publicação:
2008
Tipo de documento:
Article