PMID- 12486164 OWN - NLM STAT- MEDLINE DCOM- 20030123 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 22 IP - 24 DP - 2002 Dec 15 TI - Telomerase mediates the cell survival-promoting actions of brain-derived neurotrophic factor and secreted amyloid precursor protein in developing hippocampal neurons. PG - 10710-9 AB - 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 beta-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 approximately 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. FAU - Fu, Weiming AU - Fu W AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. FAU - Lu, Chengbiao AU - Lu C FAU - Mattson, Mark P AU - Mattson MP LA - eng PT - Journal Article PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA-Binding Proteins) RN - 0 (RNA, Messenger) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Amyloid beta-Protein Precursor/chemistry/*pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Survival/drug effects MH - Cells, Cultured MH - DNA-Binding Proteins MH - Hippocampus/cytology/*embryology/*enzymology MH - Mitogen-Activated Protein Kinases/physiology MH - Neurons/drug effects/*enzymology MH - Phosphatidylinositol 3-Kinases/physiology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Telomerase/biosynthesis/genetics/*physiology MH - Time Factors PMC - PMC6758432 EDAT- 2002/12/18 04:00 MHDA- 2003/01/24 04:00 PMCR- 2003/06/15 CRDT- 2002/12/18 04:00 PHST- 2002/12/18 04:00 [pubmed] PHST- 2003/01/24 04:00 [medline] PHST- 2002/12/18 04:00 [entrez] PHST- 2003/06/15 00:00 [pmc-release] AID - 22/24/10710 [pii] AID - 7015 [pii] AID - 10.1523/JNEUROSCI.22-24-10710.2002 [doi] PST - ppublish SO - J Neurosci. 2002 Dec 15;22(24):10710-9. doi: 10.1523/JNEUROSCI.22-24-10710.2002.