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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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2001-08, Vol.98 (18), p.10439-10444 |
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| creator | Cooper, Jonathan D. Salehi, Ahmad Delcroix, Jean-Dominique Howe, Charles L. Belichenko, Pavel V. Chua-Couzens, Jane Kilbridge, Joshua F. Carlson, Elaine J. Epstein, Charles J. Mobley, William C. |
| description | 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. |
| doi_str_mv | 10.1073/pnas.181219298 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.181219298</identifier><identifier>PMID: 11504920</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Aging - metabolism ; Aging - pathology ; Animals ; Biological Sciences ; Biological Transport, Active ; Biology ; Cell Count ; Cells ; Cholinergic Fibers - drug effects ; Cholinergic Fibers - metabolism ; Cholinergic Fibers - pathology ; Cholinergics ; Disease Models, Animal ; Down Syndrome - drug therapy ; Down Syndrome - metabolism ; Down Syndrome - pathology ; Downs syndrome ; Forebrain ; Hippocampus ; Hippocampus - metabolism ; Humans ; Infusions, Parenteral ; Internalization ; Mice ; Mice, Mutant Strains ; Nerve Degeneration - drug therapy ; Nerve Degeneration - metabolism ; Nerve Degeneration - pathology ; Nerve Growth Factor - administration & dosage ; Nerve Growth Factor - metabolism ; Neurology ; Neurons ; Neuroscience ; Phenotype ; Phenotypes ; Prosencephalon - drug effects ; Prosencephalon - metabolism ; Prosencephalon - pathology ; Receptors ; Rodents ; Septum ; Trisomy</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2001-08, Vol.98 (18), p.10439-10444</ispartof><rights>Copyright 1993-2001 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 28, 2001</rights><rights>Copyright © 2001, The National Academy of Sciences 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c631t-a03b432ef1cf2c7c713ad55548039eb41a5d4db5d54935c212bea2b97508ef2c3</citedby><cites>FETCH-LOGICAL-c631t-a03b432ef1cf2c7c713ad55548039eb41a5d4db5d54935c212bea2b97508ef2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/98/18.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3056547$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3056547$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11504920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cooper, Jonathan D.</creatorcontrib><creatorcontrib>Salehi, Ahmad</creatorcontrib><creatorcontrib>Delcroix, Jean-Dominique</creatorcontrib><creatorcontrib>Howe, Charles L.</creatorcontrib><creatorcontrib>Belichenko, Pavel V.</creatorcontrib><creatorcontrib>Chua-Couzens, Jane</creatorcontrib><creatorcontrib>Kilbridge, Joshua F.</creatorcontrib><creatorcontrib>Carlson, Elaine J.</creatorcontrib><creatorcontrib>Epstein, Charles J.</creatorcontrib><creatorcontrib>Mobley, William C.</creatorcontrib><title>Failed Retrograde Transport of NGF in a Mouse Model of Down's Syndrome: Reversal of Cholinergic Neurodegenerative Phenotypes Following NGF Infusion</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Aging - metabolism</subject><subject>Aging - pathology</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Biological Transport, Active</subject><subject>Biology</subject><subject>Cell Count</subject><subject>Cells</subject><subject>Cholinergic Fibers - drug effects</subject><subject>Cholinergic Fibers - metabolism</subject><subject>Cholinergic Fibers - pathology</subject><subject>Cholinergics</subject><subject>Disease Models, Animal</subject><subject>Down Syndrome - drug therapy</subject><subject>Down Syndrome - metabolism</subject><subject>Down Syndrome - pathology</subject><subject>Downs syndrome</subject><subject>Forebrain</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Humans</subject><subject>Infusions, Parenteral</subject><subject>Internalization</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Nerve Degeneration - drug therapy</subject><subject>Nerve Degeneration - metabolism</subject><subject>Nerve Degeneration - pathology</subject><subject>Nerve Growth Factor - administration & dosage</subject><subject>Nerve Growth Factor - metabolism</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neuroscience</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Prosencephalon - drug effects</subject><subject>Prosencephalon - metabolism</subject><subject>Prosencephalon - pathology</subject><subject>Receptors</subject><subject>Rodents</subject><subject>Septum</subject><subject>Trisomy</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktvEzEUhUcIREthywqBxQLYJPg5YyM2KJBSqRQEZW15Zu4kjhw7tWdS8jv4wzhNCI8FbGzZ9zvHvlenKB4SPCa4Yi9X3qQxkYQSRZW8VRwTrMio5ArfLo4xptVIcsqPinspLTDGSkh8tzgiRGCuKD4uvk-NddCiz9DHMIumBXQZjU-rEHsUOnRxOkXWI4M-hCFBXltw2_u34do_T-jLxrcxLOFVNlhDTOamOJkHZz3EmW3QBQwxi2aQz6a3a0Cf5uBDv1lBQtPgXLi2fnbzzpnvhmSDv1_c6YxL8GC_nxRfp-8uJ-9H5x9PzyZvzkdNyUg_MpjVnFHoSNPRpmoqwkwrhOASMwU1J0a0vK1FK7hioqGE1mBorSqBJWQFOyle73xXQ72EtgHfR-P0KtqliRsdjNV_Vryd61lYa1GqSmX5s708hqsBUq-XNjXgnPGQh6UrQlipWPlfkEgslSyrDD79C1yEIfo8A01xNpOC8wyNd1ATQ0oRusOHCdbbTOhtJvQhE1nw-Pc2f-H7EGTgyR7YCn-Wlcwe2ZCzbasv_k3obnCuh299Rh_t0EXqQzywDItS8Ir9AEm01mU</recordid><startdate>20010828</startdate><enddate>20010828</enddate><creator>Cooper, Jonathan D.</creator><creator>Salehi, Ahmad</creator><creator>Delcroix, Jean-Dominique</creator><creator>Howe, Charles L.</creator><creator>Belichenko, Pavel V.</creator><creator>Chua-Couzens, Jane</creator><creator>Kilbridge, Joshua F.</creator><creator>Carlson, Elaine J.</creator><creator>Epstein, Charles J.</creator><creator>Mobley, William C.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20010828</creationdate><title>Failed Retrograde Transport of NGF in a Mouse Model of Down's Syndrome: Reversal of Cholinergic Neurodegenerative Phenotypes Following NGF Infusion</title><author>Cooper, Jonathan D. ; 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>11504920</pmid><doi>10.1073/pnas.181219298</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aging - metabolism Aging - pathology Animals Biological Sciences Biological Transport, Active Biology Cell Count Cells Cholinergic Fibers - drug effects Cholinergic Fibers - metabolism Cholinergic Fibers - pathology Cholinergics Disease Models, Animal Down Syndrome - drug therapy Down Syndrome - metabolism Down Syndrome - pathology Downs syndrome Forebrain Hippocampus Hippocampus - metabolism Humans Infusions, Parenteral Internalization Mice Mice, Mutant Strains Nerve Degeneration - drug therapy Nerve Degeneration - metabolism Nerve Degeneration - pathology Nerve Growth Factor - administration & dosage Nerve Growth Factor - metabolism Neurology Neurons Neuroscience Phenotype Phenotypes Prosencephalon - drug effects Prosencephalon - metabolism Prosencephalon - pathology Receptors Rodents Septum Trisomy |
| title | Failed Retrograde Transport of NGF in a Mouse Model of Down's Syndrome: Reversal of Cholinergic Neurodegenerative Phenotypes Following NGF Infusion |
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