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Publication : Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development.

First Author  Zhou QG Year  2017
Journal  Stem Cell Reports Volume  9
Issue  2 Pages  543-556
PubMed ID  28757168 Mgi Jnum  J:274477
Mgi Id  MGI:6295234 Doi  10.1016/j.stemcr.2017.06.014
Citation  Zhou QG, et al. (2017) Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development. Stem Cell Reports 9(2):543-556
abstractText  The molecular mechanism of memory formation remains a mystery. Here, we show that TERT, the catalytic subunit of telomerase, gene knockout (Tert(-/-)) causes extremely poor ability in spatial memory formation. Knockdown of TERT in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. We find that TERT plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. A monosynaptic pseudotyped rabies virus retrograde tracing method shows that TERT is required for neural circuit integration of hippocampal newborn neurons. Interestingly, TERT regulated neural development and spatial memory formation in a reverse transcription activity-independent manner. Using X-ray irradiation, we find that hippocampal newborn neurons mediate the modulation of spatial memory processes by TERT. These observations reveal an important function of TERT through a non-canonical pathway and encourage the development of a TERT-based strategy to treat neurological disease-associated memory impairment.
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