Transforming growth factor beta2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits.
Neurobiol Dis
; 21(3): 568-75, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16257223
ABSTRACT
The transforming growth factor-betas (TGF-betas) regulate the induction of dopaminergic neurons and are elevated in the CSF of Parkinson's patients. We report here that mice with TGF-beta2 haploinsufficiency (TGF-beta2+/-) have subclinical defects in the dopaminergic neurons of their substantia nigra pars compacta. At 6 weeks of age, the TGF-beta2+/- mice had 12% fewer dopaminergic neurons than wild-type littermates. No additional loss of neurons occurred during the next 5 months, although striatal dopamine declined to 70% of normal. The level of 3,4-dihydroxphenylacetic acid was normal in the TGF-beta2+/- mice, indicating that a compensatory mechanism maintains dopamine stimulation of their striatum. The TGF-beta2+/- mice had normal sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, despite having reduced levels of monoamine oxidase-B. These results raise the possibility that people with naturally low levels of TGF-beta2 may have less functional reserve in their nigrostriatal pathway, causing them to be at increased risk of developing Parkinson disease.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
/
Dopamina
/
Fator de Crescimento Transformador beta
/
Fatores Etários
/
Neurônios
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Nova Zelândia