Enhanced learning in mice parallels vector-mediated nerve growth factor expression in hippocampus.
Spatial learning requires the integrity of the nerve growth factor (NGF)-responsive septohippocampal pathway. Loss of a single NGF allele at the mouse NGF locus (heterozygous null, ngf(+/-)) reduces septohippocampal NGF levels and NGF-regulated cholinergic neurotransmitter enzymes and results in spatial learning deficits in adult animals. A herpes simplex virus (HSV) amplicon vector was utilized to locally deliver NGF to the hippocampus of mice heterozygous and wild type (ngf(+/+)) at the NGF gene locus. NGF gene transfer produced transient increases in NGF protein levels and choline acetyltransferase activity in both ngf(+/-) and ngf(+/+) mice. However, spatial learning capability was improved only in ngf(+/-) mice. In aggregate, these findings suggest that amplicon-directed expression of NGF in subjects with baseline septohippocampal dysfunction can correct spatial learning deficits.
Brooks
A I
AI
Departments of Neurology and Environmental Medicine and Centers of Environmental Health Sciences and Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Cory-Slechta
D A
DA
Bowers
W J
WJ
Murg
S L
SL
Federoff
H J
HJ
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006224:Cricetinae; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics
D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase