| NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats. | |
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MedLine Citation:
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PMID: 10967308 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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R L Klein; A C Hirko; C A Meyers; J R Grimes; N Muzyczka; E M Meyer |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Brain research Volume: 875 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2002-04-11 Completed Date: 2002-05-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 144-51 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, Campus Box 100267, JHMHC, Gainesville, FL 32610-0267, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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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:
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P01 AG 10485/AG/NIA NIH HHS; P01 NS 36302/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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