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Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome
BACKGROUND: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combi...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905390/ https://www.ncbi.nlm.nih.gov/pubmed/20661276 http://dx.doi.org/10.1371/journal.pone.0011561 |
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author | Hewitt, Chelsee A. Ling, King-Hwa Merson, Tobias D. Simpson, Ken M. Ritchie, Matthew E. King, Sarah L. Pritchard, Melanie A. Smyth, Gordon K. Thomas, Tim Scott, Hamish S. Voss, Anne K. |
author_facet | Hewitt, Chelsee A. Ling, King-Hwa Merson, Tobias D. Simpson, Ken M. Ritchie, Matthew E. King, Sarah L. Pritchard, Melanie A. Smyth, Gordon K. Thomas, Tim Scott, Hamish S. Voss, Anne K. |
author_sort | Hewitt, Chelsee A. |
collection | PubMed |
description | BACKGROUND: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. CONCLUSIONS/SIGNIFICANCE: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals. |
format | Text |
id | pubmed-2905390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29053902010-07-26 Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome Hewitt, Chelsee A. Ling, King-Hwa Merson, Tobias D. Simpson, Ken M. Ritchie, Matthew E. King, Sarah L. Pritchard, Melanie A. Smyth, Gordon K. Thomas, Tim Scott, Hamish S. Voss, Anne K. PLoS One Research Article BACKGROUND: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. CONCLUSIONS/SIGNIFICANCE: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals. Public Library of Science 2010-07-16 /pmc/articles/PMC2905390/ /pubmed/20661276 http://dx.doi.org/10.1371/journal.pone.0011561 Text en Hewitt et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hewitt, Chelsee A. Ling, King-Hwa Merson, Tobias D. Simpson, Ken M. Ritchie, Matthew E. King, Sarah L. Pritchard, Melanie A. Smyth, Gordon K. Thomas, Tim Scott, Hamish S. Voss, Anne K. Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title | Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title_full | Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title_fullStr | Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title_full_unstemmed | Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title_short | Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome |
title_sort | gene network disruptions and neurogenesis defects in the adult ts1cje mouse model of down syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905390/ https://www.ncbi.nlm.nih.gov/pubmed/20661276 http://dx.doi.org/10.1371/journal.pone.0011561 |
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