Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration

J Neurosci. 1995 Apr;15(4):2819-25. doi: 10.1523/JNEUROSCI.15-04-02819.1995.


Primary fibroblasts modified to secrete nerve growth factor (NGF) were implanted into the nucleus basalis magnocellularis (NBM) of aged memory impaired rats. The NGF-producing fibroblasts survived for 6 weeks following transplantation and continued expressing NGF mRNA through the duration of the experiment. A significant amelioration of the memory impairment and a significant increase in size and number of low-affinity NGF receptor (p75)-positive neurons in the basal forebrain were observed. Implantation of NGF-producing cells into normal young adult rats resulted in a transient but significant memory impairment and hypertrophy of low-affinity NGF receptor-positive neurons. These results show that naturally occurring age-related memory loss can be reversed by grafting cells engineered to secrete NGF directly to the NBM, and that either cholinergic hyper- or hypofunction may lead to cognitive impairments.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / growth & development
  • Brain / metabolism
  • Brain / physiology*
  • Cell Transplantation*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Humans
  • Memory Disorders / therapy*
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / genetics*
  • Rats
  • Rats, Inbred F344
  • Skin / cytology
  • Skin / metabolism


  • Nerve Growth Factors