Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development

Autor: Qi-Gang Zhou, Meng-Ying Liu, Han-Woong Lee, Fuyuki Ishikawa, Sushil Devkota, Xin-Ru Shen, Xin Jin, Hai-Yin Wu, Zhigang Liu, Xiao Liu, Xun Jin, Hai-Hui Zhou, Eun Jeoung Ro, Jing Zhang, Yu Zhang, Yu-Hui Lin, Hoonkyo Suh, Dong-Ya Zhu
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Stem Cell Reports, Vol 9, Iss 2, Pp 543-556 (2017)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2017.06.014
Popis: Summary: 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. : In this article, Qi-Gang Zhou and colleagues show that spatial memory formation, neural development including dendritic development and neuritogenesis, and neural circuit integration are impaired in Tert gene knockout mice. Hippocampal TERT accounts for these phenotypes in a reverse transcription activity-independent manner. Keywords: telomerase, neural progenitor cells, hippocampus, neural development, circuit integration
Databáze: Directory of Open Access Journals