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Previous Article | Next Article
The Journal of Neuroscience, December 15, 2002, 22(24):10710-10719
Telomerase Mediates the Cell Survival-Promoting Actions of Brain-Derived Neurotrophic Factor and Secreted Amyloid Precursor Protein in Developing Hippocampal Neurons
Weiming Fu, Chengbiao Lu, and Mark P. Mattson Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224
Telomerase, a reverse transcriptase that maintains chromosome ends (telomeres) during successive cell divisions in mitotic cells is present in neuroblasts and early postmitotic embryonic neurons but is absent from adult neurons. The signals that control telomerase levels during development are unknown, as are the functions of telomerase in developing neurons. We now report that telomerase activity and levels of its catalytic subunit telomerase reverse transcriptase (TERT) are increased in embryonic hippocampal neurons by brain-derived neurotrophic factor (BDNF) and a secreted form of
-amyloid precursor protein (sAPP). BDNF and sAPP promote the survival of the embryonic neurons, and these trophic effects are blocked when TERT production is suppressed using antisense technology. Telomerase is required for the long-term survival of early postmitotic neurons during a time window of ~1 week in culture; telomerase is then downregulated and is not required for BDNF and sAPP survival signaling in mature neurons. The increase in telomerase activity and trophic effects of BDNF and sAPP are mediated by phosphatidylinositol-3 kinase and p42/p44 MAP kinases. Our findings demonstrate a requirement for telomerase in the cell survival-promoting actions of BDNF and sAPP in early postmitotic hippocampal neurons, suggesting a previously unknown role for telomerase in mediating the biological actions of neurotrophic factors during brain development.
Key words: Akt; apoptosis; insulin-like growth factor; MAP kinase; neurogenesis; TERT
Copyright © 2002 Society for Neuroscience 0270-6474/02/222410710-10$05.00/0
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