Telomerase reverse transcriptase (TERT) promotes neurogenesis after hypoxic-ischemic brain damage in neonatal rats

Neonatal hypoxic-ischemic encephalopathy (HIE) endangers quality of life in children, and curative attempts are rarely effective. Neurogenesis plays an important role in neural repair following brain damage. This study aimed to investigate the role of telomerase reverse transcriptase (TERT) in neurogenesis after neonatal hypoxic-ischemic brain damage (HIBD).

Neonatal HIBD models were established in vivo (Sprague-Dawley rats, 7 days old) and in vitro (cultured neural stem cells, NSCs). Lentivirus and adenovirus transfection was used to induce TERT overexpression. Expression of TERT was detected by quantitative real-time PCR and immunofluorescence staining. NSCs apoptosis and proliferation were measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cell counting assays, respectively. Migration and differentiation of NSCs were assessed by western blotting and immunofluorescence staining. Morris water maze test and modified neurological severity scores were conducted to evaluate the neurological function of rats.

Overexpression of TERT attenuated apoptosis of NSCs; promoted proliferation, migration, and differentiation of NSCs; and induced myelination in the brains of neonatal rats after HIBD. Moreover, it reduced the impairment of learning, memory, and neurological function after HIBD in neonatal rats. In vitro findings indicated that the expression of Gli1 was increased after OGD, and overexpression of TERT further increased the expression of Gli1 in NSCs after OGD.

TERT promotes neurogenesis and decreases neurological function injury after HIBD in neonatal rats. This neuroprotective pathway may provide a basis for developing therapeutic strategies for neonatal HIE. Furthermore, TERT may represent a target during neural injury and repair in patients with various diseases affecting the nervous system.