Document Detail


NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats.
MedLine Citation:
PMID:  10967308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Administration of nerve growth factor (NGF) by intracerebroventricular infusion or transplantation of NGF-secreting cells to the basal forebrain improves spatial memory in aged animals. Using the adeno-associated virus (AAV) vector system, basal forebrain neurons were transduced to produce NGF ectopically for long intervals (at least 9 months). Rats received intraseptal injections of either the control vector, pTR-UF4, or the pTR-NGFmyc at 3 months of age, prior to testing their performance in the Morris water task. An age-related decrease in the acquisition of the hidden platform location was found at 12 months of age in the pTR-UF4 control group, but not in the pTR-NGFmyc group. Further, when compared to 3 month old untreated animals, the control group, but not the pTR-NGFmyc group, was impaired at 12 months of age. Concomitant to preventing age-related memory deficits, the NGF gene transfer increased cholinergic neuron size by 34% in the medial septum. This approach may therefore represent a viable therapy for age-related dementia involving dysfunction in cholinergic activity and memory, such as Alzheimer's disease.
Authors:
R L Klein; A C Hirko; C A Meyers; J R Grimes; N Muzyczka; E M Meyer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  875     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2002-04-11     Completed Date:  2002-05-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  144-51     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Therapeutics, Campus Box 100267, JHMHC, Gainesville, FL 32610-0267, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging / psychology*
Animals
Behavior, Animal / drug effects,  physiology
Cell Size
Choline O-Acetyltransferase / metabolism
Gene Expression
Gene Transfer Techniques
Male
Memory / physiology
Memory Disorders / prevention & control*
Nerve Growth Factor / genetics,  pharmacology*
Neurons / cytology,  drug effects*,  enzymology
Prosencephalon / cytology,  drug effects*
Rats
Rats, Sprague-Dawley
Space Perception / physiology*
Transgenes / physiology
Grant Support
ID/Acronym/Agency:
P01 AG 10485/AG/NIA NIH HHS; P01 NS 36302/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
9061-61-4/Nerve Growth Factor; EC 2.3.1.6/Choline O-Acetyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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