The neuroprotective role of TERT via an antiapoptotic mechanism in neonatal rats after hypoxia–ischemia brain injury

Telomerase reverse transcriptase (TERT) can regulate cell apoptosis and proliferation. It has been shown that TERT expression can be induced in models of adult brain ischemia. In the present study, we investigated the role of TERT in ischemic neuronal death in neonatal hypoxic–ischemic rats model. Postnatal day 10 Sprague-Dawley rats were used to establish hypoxia–ischemia (HI) model and hypoxia alone (H) model. Pups were killed at 4, 8, 12, 24, or 48 h after the insult. Plasmid containing mock, TERT antisense or sense fragment mixed with Fugene HD was injected to the right lateral ventricle immediately after the insult respectively. Additional injection was performed after 24 h. Pups were sacrificed 24 h after the administration. TERT and cleaved caspase-3 (CC3) expression were measured by Western blot. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. We found that H/HI treatment induced neuronal apoptosis and expression of TERT and CC3. However, TERT was higher in H than in HI pups whereas CC3 and apoptosis were opposite, TERT antisense plasmid markedly attenuated TERT expression induced by HI, upregualted CC3 expression, and increased apoptosis. Our results indicate that TERT might function as an anti-apoptotic protein by inhibiting activation of caspase-3, while further studies are needed to evaluate underlying mechanisms.

► H and HI treatment increased the expression of TERT and CC3.
► We firstly found that TERT was differentially induced by hypoxia alone versus HI.
► TERT inhibition could attenuate caspase-3 activation and following apoptosis induced by HI.