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Journal of Neuroscience, Vol 15, 2819-2825, Copyright © 1995 by Society for Neuroscience
Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration
KS Chen and FH Gage
Department of Neurosciences, Genentech, Inc., South San Francisco, California 94080, USA.
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.
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