title: Telomerase reverse transcriptase upregulation attenuates astrocyte proliferation and promotes neuronal survival in the hypoxic-ischemic rat brain.
abstract: OBJECTIVE
  Telomerase reverse transcriptase (TERT) is tightly related to the resistance of cells to stress and injury. However, little is known about the roles of TERT in the nervous system. We try to investigate the effects of TERT on the function of astrocytes in developing rat brains subjected to hypoxia-ischemia.
  
  
  METHODS
  TERT expression was detected in rat brains with hypoxia-ischemia. In in vitro study, the function of astrocytes with TERT overexpression was measured, and the effects of astrocyte on neuronal apoptosis were examined. Moreover, overexpression or inhibition of TERT was conducted in vivo by gene transduction. Astrocyte proliferation was examined through Ki67 staining. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining and brain infarct volume calculation were used to detect neuronal injury.
  
  
  RESULTS
  Both TERT mRNA and protein were upregulated in neurons within 2 days but shifted to astrocytes at Day 3 after hypoxia-ischemia. Astrocyte proliferation was inhibited with TERT overexpression due to the upregulation of cell-cycle regulatory protein p15. Meanwhile, the apoptosis of neurons increased, whereas neurons were cocultured with conditioned media from astrocytes with TERT inhibition compared with TERT overexpression due to the decrease of neurotrophin-3 expression in astrocytes. Furthermore, Ki67-positive astrocytes and neuronal injury were found to be inhibited in TERT-overexpressing rat brains with hypoxia-ischemia.
  
  
  CONCLUSIONS
  TERT attenuates astrocyte proliferation and promotes neuronal survival in the developing rat brain after hypoxia-ischemia, partly through its enhancement of p15 and neurotrophin-3 expression in astrocytes.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Zhoujin
authors.initials: Z
authors.lastname: Duan
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.forename: Dapeng
authors.initials: D
authors.lastname: Wei
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Binzhi
authors.initials: B
authors.lastname: Tang
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.forename: Chunlei
authors.initials: C
authors.lastname: Yang
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D020933:Neurotrophin 3; D019098:Telomerase