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Genes 2016, 7(6), 27; doi:10.3390/genes7060027

Telomerase Activity is Downregulated Early During Human Brain Development

1
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
2
Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
3
Health Protection Research Unit, Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
4
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
5
Institute of Neurosciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Roel Ophoff
Received: 25 April 2016 / Revised: 25 May 2016 / Accepted: 6 June 2016 / Published: 16 June 2016
(This article belongs to the Special Issue Telomerase Activity in Human Cells)
View Full-Text   |   Download PDF [1282 KB, uploaded 16 June 2016]   |  

Abstract

Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. View Full-Text
Keywords: telomerase activity; brain; hTERT splice-variants; neural stem cells; hTR; expression; development telomerase activity; brain; hTERT splice-variants; neural stem cells; hTR; expression; development
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ishaq, A.; Hanson, P.S.; Morris, C.M.; Saretzki, G. Telomerase Activity is Downregulated Early During Human Brain Development. Genes 2016, 7, 27.

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