Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
<h4>Background</h4>Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease.<h4>Methodology/principal findings</h4>To understand how trisomy 21 causes these neurological abnormalities we investigated chan...
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oai:doaj.org-article:9f51062a00a048609ce9234d5876a4cf2021-12-02T20:20:01ZGene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.1932-620310.1371/journal.pone.0011561https://doaj.org/article/9f51062a00a048609ce9234d5876a4cf2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20661276/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Chelsee A HewittKing-Hwa LingTobias D MersonKen M SimpsonMatthew E RitchieSarah L KingMelanie A PritchardGordon K SmythTim ThomasHamish S ScottAnne K VossPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11561 (2010) |
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Medicine R Science Q Chelsee A Hewitt King-Hwa Ling Tobias D Merson Ken M Simpson Matthew E Ritchie Sarah L King Melanie A Pritchard Gordon K Smyth Tim Thomas Hamish S Scott Anne K Voss Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome. |
| description |
<h4>Background</h4>Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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 |
article |
| author |
Chelsee A Hewitt King-Hwa Ling Tobias D Merson Ken M Simpson Matthew E Ritchie Sarah L King Melanie A Pritchard Gordon K Smyth Tim Thomas Hamish S Scott Anne K Voss |
| author_facet |
Chelsee A Hewitt King-Hwa Ling Tobias D Merson Ken M Simpson Matthew E Ritchie Sarah L King Melanie A Pritchard Gordon K Smyth Tim Thomas Hamish S Scott Anne K Voss |
| author_sort |
Chelsee A Hewitt |
| title |
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_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_sort |
gene network disruptions and neurogenesis defects in the adult ts1cje mouse model of down syndrome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/9f51062a00a048609ce9234d5876a4cf |
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