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. 1999 Mar;90(3):815-21. doi: 10.1016/s0306-4522(98)00537-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Choline O-Acetyltransferase / metabolism*
  • Dependovirus / genetics
  • Gene Expression / physiology
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / pharmacology*
  • Prosencephalon / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor / metabolism*
  • Recombination, Genetic
  • Time Factors
  • Transgenes / genetics


  • Brain-Derived Neurotrophic Factor
  • Luminescent Proteins
  • Nerve Growth Factors
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • Green Fluorescent Proteins
  • Choline O-Acetyltransferase
  • Receptor Protein-Tyrosine Kinases