Long-term actions of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and Trk receptor levels in the adult rat basal forebrain.
Neuroscience
; 90(3): 815-21, 1999 Mar.
Article
em En
| MEDLINE
| ID: mdl-10218782
ABSTRACT
Trophic factor gene therapy may provide a rational treatment strategy for neurodegenerative disease. Recombinant adeno-associated virus vectors, incorporating a neuron-specific promoter driving bicistronic expression of green fluorescent protein and either nerve growth factor or brain-derived neurotrophic factor, transduced 10,000-15,000 neurons in the medial septum for periods of at least six months. Both cholinergic and non-cholinergic neurons expressed green fluorescent protein. Nerve growth factor and brain-derived neurotrophic factor vectors produced up to 50% increases in immunohistochemical detection of the acetylcholine-synthesizing enzyme in septal neurons ipsilateral to the injection. Increased levels of this enzyme, choline acetyltransferase, persisted for six months with the brain-derived neurotrophic factor vector. The nerve growth factor vector increased Trk receptor immunoreactivity in a volume of brain exceeding that of the transduced cells. Counterstaining for the neuronal marker, NeuN, or Nissl substance did not reveal any vector toxicity at any time-point. It therefore appears that the lasting effects of vector-mediated trophic factor gene transfer will offer a new approach for modulating septal cholinergic transmission and Trk receptor activity.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Colina O-Acetiltransferase
/
Prosencéfalo
/
Receptores de Fator de Crescimento Neural
/
Receptores Proteína Tirosina Quinases
/
Fator Neurotrófico Derivado do Encéfalo
/
Fatores de Crescimento Neural
Limite:
Animals
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article