Failed retrograde transport of NGF in a mouse model of Down's syndrome

Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

J. D. Cooper, A. Salehi, J. D. Delcroix, Charles L Howe, P. V. Belichenko, J. Chua-Couzens, J. F. Kilbridge, E. J. Carlson, C. J. Epstein, W. C. Mobley

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10439-10444
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number18
DOIs
StatePublished - Aug 28 2001
Externally publishedYes

Fingerprint

Nerve Growth Factor
Down Syndrome
Cholinergic Neurons
Cholinergic Agents
Phenotype
Alzheimer Disease
Trisomy
Diploidy
Hippocampus
Basal Forebrain
Neurons

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Failed retrograde transport of NGF in a mouse model of Down's syndrome : Reversal of cholinergic neurodegenerative phenotypes following NGF infusion. / Cooper, J. D.; Salehi, A.; Delcroix, J. D.; Howe, Charles L; Belichenko, P. V.; Chua-Couzens, J.; Kilbridge, J. F.; Carlson, E. J.; Epstein, C. J.; Mobley, W. C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 18, 28.08.2001, p. 10439-10444.

Research output: Contribution to journalArticle

Cooper, J. D. ; Salehi, A. ; Delcroix, J. D. ; Howe, Charles L ; Belichenko, P. V. ; Chua-Couzens, J. ; Kilbridge, J. F. ; Carlson, E. J. ; Epstein, C. J. ; Mobley, W. C. / Failed retrograde transport of NGF in a mouse model of Down's syndrome : Reversal of cholinergic neurodegenerative phenotypes following NGF infusion. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 18. pp. 10439-10444.
@article{e057d0f387344e0ea4f8ed3d18bdaaba,
title = "Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion",
abstract = "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.",
author = "Cooper, {J. D.} and A. Salehi and Delcroix, {J. D.} and Howe, {Charles L} and Belichenko, {P. V.} and J. Chua-Couzens and Kilbridge, {J. F.} and Carlson, {E. J.} and Epstein, {C. J.} and Mobley, {W. C.}",
year = "2001",
month = "8",
day = "28",
doi = "10.1073/pnas.181219298",
language = "English (US)",
volume = "98",
pages = "10439--10444",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Failed retrograde transport of NGF in a mouse model of Down's syndrome

T2 - Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

AU - Cooper, J. D.

AU - Salehi, A.

AU - Delcroix, J. D.

AU - Howe, Charles L

AU - Belichenko, P. V.

AU - Chua-Couzens, J.

AU - Kilbridge, J. F.

AU - Carlson, E. J.

AU - Epstein, C. J.

AU - Mobley, W. C.

PY - 2001/8/28

Y1 - 2001/8/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=2942591228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942591228&partnerID=8YFLogxK

U2 - 10.1073/pnas.181219298

DO - 10.1073/pnas.181219298

M3 - Article

VL - 98

SP - 10439

EP - 10444

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -