Failed Retrograde Transport of NGF in a Mouse Model of Down's Syndrome: Reversal of Cholinergic Neurodegenerative Phenotypes Following NGF Infusion
Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive c...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 18; pp. 10439 - 10444 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
28.08.2001
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive changes in the hippocampal terminal fields of these neurons with respect to diploid controls. The changes were associated with significantly impaired retrograde transport of nerve growth factor (NGF) from the hippocampus to the basal forebrain. Intracerebroventricular NGF infusion reversed well established abnormalities in BFCN size and number and restored the deficit in cholinergic innervation. The findings are evidence that even BFCNs chronically deprived of endogenous NGF respond to an intervention that compensates for defective retrograde transport. We suggest that age-related cholinergic neurodegeneration may be a treatable disorder of failed retrograde NGF signaling. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 J.D.C. and A.S. contributed equally to this work. To whom reprint requests should be sent at the present address: Department of Neuropathology, Institute of Psychiatry, King's College, London SE5 8AF, United Kingdom. E-mail: j.cooper@iop.kcl.ac.uk. Edited by Dominick P. Purpura, Albert Einstein College of Medicine, Bronx, NY, and approved July 3, 2001 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.181219298 |