Abstract
Neonatal hypoxic ischemic encephalopathy (HIE) endangers quality of life in children; but effective cure is rare. Neurogenesis plays an important role in neural repair following brain damage. Recent studies have demonstrated that telomerase reverse transcriptase (TERT) was involved in neurogenesis regulation. However, whether TERT participates in the regulation of neurogenesis after hypoxic-ischemic brain damage (HIBD) is unclear. Here, we established a model of HIBD in neonatal rats both in vivo and in vitro, and used lentivirus and adenovirus transfection for TERT overexpression to investigate its role in neurogenesis after HIBD in developmental stage. Using immunofluorescence staining, cell counting Kit-8 staining, TUNEL, and western blotting, we observed that TERT attenuated apoptosis and promoted proliferation, migration, and differentiation in neural stem cells (NSCs). Furthermore, TERT induced myelination in the brain of neonatal rats after HIBD. Neurobehavioral tests revealed that TERT could improve learning, memory, and neurological function after HIBD in neonatal rats, and thus promote the recovery of neurological function after HIBD. In addition, we investigated the regulatory mechanism of TERT during neurogenesis after HIBD in developmental stage. We found that TERT may regulate neurogenesis after HIBD through the Sonic Hedgehog/Gli1 signaling pathway. Our study demonstrated that TERT could promote neural repair and neurological function recovery after HIBD in neonatal rats. The new neuroprotective pathway regulated by TERT during HIBD described here could provide a basis for developing therapeutic strategy for neonatal HIE. Furthermore, TERT may be a potential target during neural repair and reconstruction in various diseases affecting nervous system.
TERT Promotes Neurogenesis and Neural Repair after Hypoxic Ischemic Brain Damage in Neonatal Rats