Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration.
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.
Chen
K S
KS
Department of Neurosciences, Genentech, Inc., South San Francisco, California 94080, USA.
Gage
F H
FH
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008569:Memory Disorders / Q000628:therapy*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000166:cytology / Q000378:metabolism
D009414:Nerve Growth Factors